Pathogens, Год журнала: 2024, Номер 13(11), С. 1003 - 1003
Опубликована: Ноя. 15, 2024
(
Cell, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
3
Cancer Letters, Год журнала: 2023, Номер 580, С. 216481 - 216481
Опубликована: Ноя. 15, 2023
Small extracellular vesicles (sEVs) such as exosomes are nanoscale membranous particles (<200 nm) that have emerged crucial targets for liquid biopsy and promising drug delivery vehicles. They play a significant role in tumor progression intercellular messengers. can serve biomarkers diagnosis carriers cancer treatment. This article reviews recent studies on sEVs oncology explores their potential Following tumorigenesis, the microenvironment (TME) circulatory system undergo modifications to regulate various events TME, including angiogenesis, epithelial-mesenchymal transition (EMT), immunity, with either pro- or anti-tumor effects. been investigated use diagnostic prognostic variety of tumors, lung cancer, melanoma, breast prostate hepatocellular carcinoma. be used therapy by packaging drugs proteins into them through pre- post-isolation modification techniques. The clinical trials also summarized. Finally, challenges described possible approaches tackling suggested. Overall, will advance precision medicine has shown great applications.
Язык: Английский
Процитировано
29
Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115195 - 115195
Опубликована: Фев. 5, 2024
Enhanced targeting approaches will support the treatment of diseases associated with dysfunctional mitochondria, which play critical roles in energy generation and cell survival. Obstacles to mitochondria-specific include presence distinct biological barriers need pass through (or avoid) various internalization mechanisms. A range studies have reported design mitochondrially-targeted nanomedicines that navigate complex routes required influence mitochondrial function; nonetheless, a significant journey lies ahead before become suitable for clinical use. Moving swiftly forward require safety studies, vivo assays confirming effectiveness, methodologies validate mitochondria-targeted nanomedicines' subcellular location/activity. From nanomedicine standpoint, we describe involved (from administration arrival within mitochondria), features influencing rational design, techniques used identify/validate successful targeting. Overall, rationally-designed mitochondria-targeted-based hold great promise precise therapeutic delivery.
Язык: Английский
Процитировано
11
BioEssays, Год журнала: 2025, Номер unknown
Опубликована: Фев. 26, 2025
Talin, a key integrin activator, is essential for cellular adhesion, signal transduction, and mechanical stability. Its transition between autoinhibited active conformations allows dynamic regulation of adhesion in response to environmental cues. Cholesterol-rich membrane microdomains, such as lipid rafts, organize stabilize signaling platforms, influencing talin conformational states. Cholesterol switch modulating activation, binding, adhesion. Environmental pollutants, including heavy metals air toxins, disrupt cholesterol homeostasis, destabilize interfere with talin-integrin interactions. These disruptions impair tissue repair, fidelity, contributing atherosclerosis cancer metastasis. Understanding talin's interaction cholesterol-rich domains offers critical insights into reveals the broader impact toxicants on function. This framework emphasizes importance composition, particularly cholesterol, mediating effects stressors suggests potential therapeutic interventions.
Язык: Английский
Процитировано
1
Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(7)
Опубликована: Июль 1, 2024
Abstract Extracellular vesicles (EVs) are shed from the plasma membrane, but regulation and function of these EVs remain unclear. We found that oxidative stress induced by H 2 O in Hela cells stimulated filopodia formation secretion EVs. were small (150 nm) labeled for CD44, indicating they derived filopodia. Filopodia‐derived (sEVs) enriched with sphingolipid ceramide, consistent increased ceramide membrane Ceramide was colocalized neutral sphingomyelinase (nSMase2) acid (ASM), two sphingomyelinases generating at membrane. Inhibition nSMase2 ASM prevented stress‐induced sEV shedding only inhibition formation. S‐palmitoylated interacted to generate shedding. sEVs contained decreased level enzymes oxidatively stressed cells. A novel metabolic labeling technique showed fluorescent NBD‐ceramide. NBD‐ceramide‐labeled transported mitochondria, ultimately inducing cell death a proportion neuronal (N2a) In conclusion, using we provide evidence induces interaction filopodia, which leads ceramide‐rich target mitochondria propagate death.
Язык: Английский
Процитировано
7
Cancer Science, Год журнала: 2024, Номер 115(6), С. 1726 - 1737
Опубликована: Март 26, 2024
Abstract Tumor tissue is densely packed with cancer cells, non‐cancerous and ECM, forming functional structures. Cancer cells transfer extracellular vesicles (EVs) to modify surrounding normal into cancer‐promoting establishing a tumor‐favorable environment together other signaling molecules structural components. Such environments largely affect cell properties, so as EV‐mediated cellular communications within tumor tissue. However, current research on EVs focuses analysis of isolated from the liquid phase, including culture supernatants blood draws, 2D‐cultured assays, or systemic analyses animal models for biodistribution. Therefore, we have limited understanding local EV tissues. In this review, discuss need study in physiological context by summarizing findings impacts properties techniques required analysis. likely alter pose physical barriers, interactions, interstitial flows dynamics, introduce varieties types taken up. Utilizing experimental settings spatial analyses, tackle remaining questions cancer–host interactions. Understanding tissues will lead developing interaction‐targeting therapies provide insight interspecies
Язык: Английский
Процитировано
6
Epilepsia, Год журнала: 2025, Номер unknown
Опубликована: Фев. 18, 2025
Abstract Soticlestat (TAK‐935) is a potent and selective inhibitor of cholesterol 24‐hydroxylase (CYP46A1), an enzyme primarily expressed in the brain that catabolizes to 24 S ‐hydroxycholesterol (24HC). In ELEKTRA phase II clinical trial, soticlestat reduced seizure frequency patients with developmental epileptic encephalopathies, two III studies evaluating safety efficacy Dravet syndrome (SKYLINE) Lennox–Gastaut (SKYWAY) have recently been completed. The exact mechanism action by which exerts pharmacological benefits remains undetermined. this review, we assess available preclinical evidence present working hypothesis for antiseizure effects soticlestat. data support three potential mechanisms action: (1) normalization threshold via reduction 24HC levels brain; as acts positive allosteric modulator glutamate N‐methyl‐D‐aspartate receptors, may lead decreased hyperexcitability elevated thresholds; (2) restoration sequestration from synaptic cleft; accumulation cleft enhances neural excitation can contribute neurotoxicity; inhibit conversion membrane lipid raft microdomain help preserve it, consequently reducing excessive excitation; (3) suppression neuroinflammation inflammatory cytokine release. These warrant further investigation.
Язык: Английский
Процитировано
0
Molecular Biology of the Cell, Год журнала: 2025, Номер 36(4)
Опубликована: Фев. 19, 2025
Cytoplasmic K63-linked polyubiquitin signals have well-established roles in endocytosis and selective autophagy. However, how these help to direct different cargos intracellular trafficking routes is unclear. Here we report that, when the K63-polyubiquitin signal blocked by expression of a high-affinity sensor (named Vx3), many proteins originating from plasma membrane are found trapped clusters small vesicles that colocalize with ATG9A, transmembrane protein plays an essential role Importantly, whereas ATG9A required for cluster formation, other core autophagy machinery as well cargo receptors not required. Although sequestered vesicular ATG9-dependent manner, additional needed induce LC3 conjugation. Upon removal Vx3 block, K63-polyubiquitylated rapidly delivered lysosomes. These observations suggest unexpected K63-polyubiquitin–modified proteins.
Язык: Английский
Процитировано
0
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 25, 2025
Язык: Английский
Процитировано
0
Biomimetics, Год журнала: 2025, Номер 10(3), С. 141 - 141
Опубликована: Фев. 25, 2025
Cardiomyopathies, a cause of heart failure, are predominant death globally and may lead to discernible myocardial abnormalities. Several therapeutic agents were discovered, developed, investigated, evaluated save patients’ lives improve their quality life. The effective administration drugs improves outcomes while reducing side effects. Nanoparticles (NPs) have been utilised for the delivery demonstrate promise in ischaemia/reperfusion injury. However, significant limitations NPs include non-specific targeting immunogenicity. To cardiac biocompatibility, surface modifications using cell membrane (cCM) coating on hypothesised. Here, cCMs isolated from human ventricular line (AC16), mesoporous silica nanoparticles (MSNs) synthesised then coated with cCMs. membrane-coated (cCMCMSNs) did not significantly alter encapsulation efficiency or release profile loaded drug (Rhodamine B) comparison MSN. Moreover, cCMCMSNs demonstrated enhanced distribution RhB specifically cells, compared other types, without causing cytotoxicity. evaluate immune escape, exposed activated macrophages, demonstrating that phagocytosed lesser extent than This study synthesis membranes as nanomedicine technologies enhance selective potentially offering an alternate method cardiovascular diseases.
Язык: Английский
Процитировано
0