Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)

Published: April 7, 2024

Abstract Brain disorders represent a significant challenge in medical science due to the formidable blood–brain barrier (BBB), which severely limits penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into innovative realm biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential circumvent BBB's restrictions. By mimicking native properties, these nanocarriers emerge as promising solution for enhancing drug delivery brain, offering strategic advantage overcoming barrier's selective permeability. The unique benefits leveraging membranes from various sources is evaluated advanced technologies fabricating membrane‐encapsulated nanoparticles capable masquerading endogenous cells are examined. enables targeted broad spectrum therapeutic agents, ranging small molecule drugs proteins, thereby providing an approach neurocare. Further, contrasts capabilities limitations with traditional methods, underlining enable targeted, sustained, minimally invasive modalities. concluded perspective on clinical translation underscoring transformative impact landscape intractable brain diseases.

Language: Английский

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Transient receptor potential melastatin 7 cation channel, magnesium and cell metabolism in vascular health and disease

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 12, 2025

Abstract Preserving the balance of metabolic processes in endothelial cells (ECs) and vascular smooth muscle (VSMCs), is crucial for optimal function integrity. ECs are metabolically active depend on aerobic glycolysis to efficiently produce energy their essential functions, which include regulating tone. Impaired EC metabolism linked damage, increased permeability inflammation. Metabolic alterations VSMCs also contribute dysfunction atherosclerosis hypertension. Magnesium (Mg 2+ ) second most abundant intracellular divalent cation influences molecular that regulate function, including vasodilation, vasoconstriction, release vasoactive substances. Mg critically involved maintaining cellular homeostasis since it an cofactor ATP, nucleic acids hundreds enzymes processes. Low levels have been dysfunction, tone, inflammation arterial remodeling. Growing evidence indicates important role transient receptor potential melastatin‐subfamily member 7 (TRPM7) channel regulation VSMCs. In vasculature, TRPM7 deficiency leads impaired contraction, phenotypic switching VSMCs, fibrosis, characterize phenotype Here we provide a comprehensive overview TRPM7/Mg how VSMC such as glucose homeostasis, redox regulation, phosphoinositide signaling, mineral metabolism. The putative altered hypertension discussed.

Language: Английский

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Interplay of fatty acids, insulin and exercise in vascular health

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 7, 2025

Fatty acid metabolism, exercise, and insulin action play critical roles in maintaining vascular health, especially relevant metabolic disorders such as obesity, type 2 diabetes, cardiovascular disease. Insulin, a vasoactive hormone, induces arterial vasodilation throughout the tree, increasing compliance enhancing tissue perfusion. These effects, however, are impaired individuals with obesity evidence suggests that resistance contributes to pathogenesis of diabetes its complications. Elevated plasma levels free fatty acids people engender inflammation, endothelial dysfunction, resistance. Importantly, these effects both functionally structurally dependent, saturated primary culprits, while polyunsaturated may support sensitivity function. Exercise enhances oxidation, reduces circulating acids, improves sensitivity, thereby mitigating lipotoxicity promoting Additionally, exercise beneficial adaptations. This review examines complex interplay among training-induced adaptations, insulin-mediated changes, highlighting their collective impact on health underlying mechanisms healthy insulin-resistant states. It also explores therapeutic potential targeted prescriptions acid-focused dietary strategies for emphasizing tailored interventions maximize benefits. Future research should investigate pathways linking metabolism resistance, focus how modifications can be personalized enhance optimize reduce risks associated

Language: Английский

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Fibrometabolism—An emerging therapeutic frontier in pulmonary fibrosis

Science Signaling, Journal Year: 2021, Volume and Issue: 14(697)

Published: Aug. 24, 2021

Metabolic reprogramming of myofibroblasts promotes fibrosis and could be targeted to treat fibrotic diseases.

Language: Английский

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Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(5)

Published: Jan. 23, 2024

Flow patterns exert significant effects on vascular endothelial cells (ECs) to lead the focal nature of atherosclerosis. Using a step flow chamber investigate disturbed shear (DS) and pulsatile (PS) ECs in same channel, we conducted single-cell RNA sequencing analyses explore distinct transcriptomic profiles regulated by DS vs. PS. Integrated analysis identified eight cell clusters demonstrated that induces EC transition from atheroprotective proatherogenic phenotypes. an automated type annotation algorithm (SingleR), showed promoted endothelial-to-mesenchymal (EndMT) inducing transcriptional phenotypes for inflammation, hypoxia responses, transforming growth factor-beta (TGF-β) signaling, glycolysis, fatty acid synthesis. Enolase 1 (ENO1), key gene was one top-ranked genes DS-induced EndMT cluster. Pseudotime trajectory revealed kinetic expression ENO1 significantly associated with silencing repressed DS- TGF-β-induced inflammation EndMT. Consistent these findings, highly expressed at inner curvature mouse aortic arch (which is exposed DS) atherosclerotic lesions, suggesting its role vivo. In summary, present comprehensive atlas response different within channel. Among DS-regulated genes, plays important These results provide insights into how hemodynamic forces regulate endothelium health disease.

Language: Английский

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Gut Microbiota–Tumor Microenvironment Interactions: Mechanisms and Clinical Implications for Immune Checkpoint Inhibitor Efficacy in Cancer

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 171 - 192

Published: Jan. 1, 2025

Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade detection. Although have shown promising results, especially solid tumors, patient responses vary widely due multiple intrinsic and extrinsic factors within tumor microenvironment. Emerging evidence suggests gut microbiota plays pivotal role modulating at site may even influence outcomes patients receiving ICIs. This review explores complex interactions between microenvironment, examining how these could impact effectiveness of ICI therapy. Furthermore, we discuss dysbiosis, an imbalance composition, contribute resistance ICIs, highlight microbiota-targeted strategies potentially overcome this challenge. Additionally, studies investigating diagnostic potential profiles patients, considering microbial markers might aid early detection stratification By integrating insights from preclinical clinical studies, aim shed light on microbiome modulation adjunct tool, paving way for personalized approaches optimize outcomes.

Language: Английский

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Endothelial dysfunction in cardiovascular diseases: mechanisms and in vitro models

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Endothelial cells (ECs) are arranged side-by-side to create a semi-permeable monolayer, forming the inner lining of every blood vessel (micro and macrocirculation). Serving as first barrier for circulating molecules cells, ECs represent main regulators vascular homeostasis being able respond environmental changes, either physical or chemical signals, by producing several factors that regulate tone cellular adhesion. Healthy endothelium has anticoagulant properties prevent adhesion leukocytes platelets walls, contributing resistance thrombus formation, regulating inflammation, smooth muscle cell proliferation. Many risk cardiovascular diseases (CVDs) promote endothelial expression chemokines, cytokines, molecules. The resultant activation can lead dysfunction (ECD). In vitro models ECD allow study molecular mechanisms disease provide research platform screening potential therapeutic agents. Even though alternative available, such animal ex vivo models, in offer higher experimental flexibility reproducibility, making them valuable tool understanding pathophysiological diseases, CVDs. Therefore, this review aims synthesize currently available regarding ECD, emphasizing This work will focus on 2D culture (endothelial lines primary ECs), 3D systems (scaffold-free scaffold-based), (such organ-on-a-chip). We dissect role external stimuli—chemical mechanical—in triggering ECD.

Language: Английский

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Scalable Generation of Nanovesicles from Human-Induced Pluripotent Stem Cells for Cardiac Repair

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14334 - 14334

Published: Nov. 18, 2022

Extracellular vesicles (EVs) from stem cells have shown significant therapeutic potential to repair injured cardiac tissues and regulate pathological fibrosis. However, scalable generation of derived EVs for clinical utility remains a huge technical challenge. Here, we report rapid size-based extrusion strategy generate EV-like membranous nanovesicles (NVs) easily sourced human iPSCs in large quantities (yield 900× natural EVs). NVs isolated using density-gradient separation (buoyant density 1.13 g/mL) are spherical shape morphologically intact readily internalised by cardiomyocytes, primary fibroblasts, endothelial cells. captured the dynamic proteome parental include pluripotency markers (LIN28A, OCT4) regulators processes, including tissue (GJA1, HSP20/27/70, HMGB1), wound healing (FLNA, MYH9, ACTC1, ILK), stress response/translation initiation (eIF2S1/S2/S3/B4), hypoxia response (HMOX2, HSP90, GNB1), extracellular matrix organization (ITGA6, MFGE8, ITGB1). Functionally, significantly promoted tubule formation (angiogenesis) (p < 0.05) survival cardiomyocytes exposed low oxygen conditions (hypoxia) 0.0001), as well attenuated TGF-β mediated activation fibroblasts 0.0001). Quantitative profiling target cell following NV treatments revealed upregulation angiogenic proteins (MFGE8, MYH10, VDAC2) pro-survival (CNN2, THBS1, IGF2R) cardiomyocytes. In contrast, TGF-β-driven remodelling capacity (ACTN1, COL1A1/2/4A2/12A1, ITGA1/11, THBS1). This study presents approach generating functional repair.

Language: Английский

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Mitochondrial ATP Production is Required for Endothelial Cell Control of Vascular Tone

Function, Journal Year: 2022, Volume and Issue: 4(2)

Published: Dec. 9, 2022

Abstract Arteries and veins are lined by nonproliferating endothelial cells that play a critical role in regulating blood flow. Endothelial also regulate tissue perfusion, metabolite exchange, thrombosis. It is thought rely on ATP generated via glycolysis, rather than mitochondrial oxidative phosphorylation, to fuel each of these energy-demanding processes. However, metabolism has mainly been studied the context proliferative cells, little known about energy production within fully formed vascular wall. Using intact arteries isolated from rats mice, we show inhibiting respiration disrupts control tone. Basal, mechanically activated, agonist-evoked calcium activity artery prevented synthesis. Agonist-evoked was inhibited blocking transport pyruvate, master for production, through pyruvate carrier. The mitochondria cell independent species, sex, or bed. These data supply necessary calcium-dependent, nitric oxide-mediated tone, identifies fueling perfused vessel function.

Language: Английский

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Canagliflozin mitigates carfilzomib-induced endothelial apoptosis via an AMPK-dependent pathway

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114907 - 114907

Published: May 27, 2023

Carfilzomib (CFZ) is a proteasome inhibitor approved for relapsed/refractory multiple myeloma (MM) but its clinical use limited by cardiovascular toxicity. The mechanisms of CFZ-induced toxicity are not fully understood endothelial dysfunction may be common denominator. Here, we first characterized the direct toxic effects CFZ on cells (HUVECs and EA.hy926 cells) tested whether SGLT2 inhibitors, known to have cardioprotective effects, can protect against To determine chemotherapeutic effect in presence MM lymphoma were treated with or without canagliflozin. decreased cell viability induced apoptotic death concentration-dependent manner. also upregulated ICAM-1 VCAM-1 downregulated VEGFR-2. These associated activation Akt MAPK pathways, inhibition p70s6k, downregulation AMPK. Canagliflozin, empagliflozin dapagliflozin, protected from apoptosis. Mechanistically, canagliflozin abrogated JNK AMPK inhibition. AICAR (an activator) apoptosis, compound C inhibitor) protective canagliflozin, strongly suggesting that mediates these effects. Canagliflozin did interfere anticancer cancer cells. In conclusion, our findings demonstrate time signaling changes. an AMPK-dependent mechanism, interfering cytotoxicity

Language: Английский

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