Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Окт. 9, 2023

Abstract The use of nanotechnology has the potential to revolutionize detection and treatment cancer. Developments in protein engineering materials science have led emergence new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers medicinal purposes been approved human trials, only a few authorized clinical cells. In this review, we analyze some formulations discuss challenges translating findings from lab clinic. This study highlights various compounds that can be used selective tumor inherent difficulties therapy. Nanotechnology provides promising platform improving future, but further research is needed overcome current limitations translation. Graphical

Язык: Английский

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Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

Acta Pharmacologica Sinica, Год журнала: 2022, Номер 44(4), С. 695 - 709

Опубликована: Окт. 17, 2022

Язык: Английский

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Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Авг. 2, 2022

Abstract Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative and cancers, particularly CVD which accumulation lipids (mainly cholesteryl esters) within macrophage/foam cells underneath endothelial layer drives formation atherosclerotic lesions eventually. More more studies have shown that lowering level, especially low-density lipoprotein protects system prevents events effectively. Maintaining is determined by biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All processes should be precisely controlled regulatory pathways. Based on regulation homeostasis, many interventions been developed to lower inhibiting biosynthesis uptake or enhancing utilization Herein, we summarize historical review research events, current understandings molecular pathways playing key regulating cholesterol-lowering clinics preclinical well new targets their clinical advances. importantly, discuss benefits those for treatment including obesity, diabetes, nonalcoholic fatty liver disease, cancer, osteoporosis virus infection.

Язык: Английский

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Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications

Frontiers in Medicine, Год журнала: 2022, Номер 8

Опубликована: Янв. 20, 2022

Endothelium plays a fundamental role in the cardiovascular system, forming an interface between blood and adjacent tissues by regulating vascular tone through synthesis of nitric oxide, prostaglandins other relaxing factors. Endothelial dysfunction is characterized vasoconstriction, cell proliferation shifting toward proinflammatory prothrombic state. In hypertension endothelial may be involved initiation development inflammation, remodeling, atherosclerosis independently associated with increased risk. Different conditions such as impaired shear stress, inflammation oxidative activation renin angiotensin system have been described important pathophysiological mechanisms dysfunction. The release extracellular vesicles neighboring cells wall has emerged regulator function potential antihypertensive properties beneficial effects counteracting mediated organ damage. Furthermore, macrovesicles are emerging innovative therapeutic approach for protection, allowing delivery bioactive molecules, miRNA drugs interacting system. this review we summarize available evidence about implications diseases, focusing on its sequelae, strategies targeting endothelium aim to improve remodeling.

Язык: Английский

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Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Июнь 1, 2022

Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There compelling evidence suggesting numerous modifications including the change of size, density, biochemical properties in low-density lipoprotein (LDL) within vascular wall. These LDL, addition to LDL transcytosis retention, contribute initiation, development clinical consequences atherosclerosis. Among different atherogenic oxidation represents a primary modification. A series pathophysiological changes caused by oxidized (oxLDL) enhance formation foam cells atherosclerotic plaques. OxLDL also promotes fatty streaks atherogenesis through induction endothelial dysfunction, cells, monocyte chemotaxis, proliferation migration SMCs, platelet activation, which culminate plaque instability ultimately rupture. This article provides concise review oxLDL, enzymes mediating oxidation, receptors pro-atherogenic signaling pathways oxLDL cells. The explores how functions stages dysfunction Future targeted therapies aiming at reducing and/or lowering levels oxLDL-mediated pro-inflammatory responses are discussed.

Язык: Английский

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Resveratrol and endothelial function: A literature review

Pharmacological Research, Год журнала: 2021, Номер 170, С. 105725 - 105725

Опубликована: Июнь 10, 2021

Язык: Английский

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Hypertension, Neurovascular Dysfunction, and Cognitive Impairment

Hypertension, Год журнала: 2022, Номер 80(1), С. 22 - 34

Опубликована: Окт. 5, 2022

Hypertension affects a significant proportion of the adult and aging population represents an important risk factor for vascular cognitive impairment late-life dementia. Chronic high blood pressure continuously challenges structural functional integrity cerebral vasculature, leading to microvascular rarefaction dysfunction, neurovascular uncoupling that typically impairs supply. disrupts blood-brain barrier integrity, promotes neuroinflammation, may contribute amyloid deposition Alzheimer pathology. The mechanisms underlying these harmful effects are still focus investigation, but studies in animal models have provided molecular cellular mechanistic insights. Remaining questions relate whether adequate treatment hypertension prevent deterioration function, threshold treatment, most effective antihypertensive drugs. Recent advances biology, advanced brain imaging, detection subtle behavioral phenotypes begun provide insights into critical issues. Importantly, parallel analysis parameters humans is feasible, making it possible foster translational advancements. In this review, we evaluation evidence available experimental examine progress made identify remaining gaps knowledge.

Язык: Английский

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Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Дек. 22, 2021

Atherosclerosis, the chronic accumulation of cholesterol-rich plaque within arteries, is associated with a broad spectrum cardiovascular diseases including myocardial infarction, aortic aneurysm, peripheral vascular disease, and stroke. Atherosclerotic disease remains leading cause mortality in high-income countries recent years have witnessed notable increase prevalence low- middle-income regions world. Considering this prominent evolving global burden, there need to identify cellular mechanisms that underlie pathogenesis atherosclerosis discover novel therapeutic targets for preventing or mitigating its clinical sequelae. Despite decades research, we still do not fully understand complex cell-cell interactions drive atherosclerosis, but new investigative approaches are rapidly shedding light on these essential mechanisms. The endothelium resides at interface systemic circulation underlying vessel wall plays an role governing pathophysiological processes during atherogenesis. In review, present emerging evidence implicates activated as driver by directing site-specificity formation promoting development through intracellular processes, which regulate endothelial cell proliferation turnover, metabolism, permeability, plasticity. Moreover, highlight intercellular communication cells modulate activity key populations involved atherogenesis, discuss how contribute resolution biology - process dysregulated advanced plaques. Finally, describe important future directions preclinical epigenetic targeted therapies, limit progression at-risk affected patients.

Язык: Английский

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Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation

Circulation Research, Год журнала: 2022, Номер 130(7), С. 1038 - 1055

Опубликована: Фев. 24, 2022

Background: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation migration impaired angiogenesis in the ischemic hindlimbs of adult mice. However, role underlying mechanisms atherosclerosis remain unclear. Methods: Mouse models cell (EC)-specific-Bach1 knockout mice were used to study regulation atherogenesis mechanisms. Results: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with gene expression carotid plaques from patients. upregulated ECs human mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced lesions, macrophage content plaques, adhesion molecules (ICAM1 [intercellular molecule-1] VCAM1 [vascular molecule-1]), reduced plasma TNF-α (tumor necrosis factor-α) IL-1β levels deletion knockdown inhibited monocyte–endothelial oscillatory shear stress TNF-α-mediated induction and/or proinflammatory cytokines ECs, umbilical vein aortic ECs. Mechanistic studies showed upon stimulation, YAP (yes-associated protein) induced translocated into nucleus by binding promoter. formed a complex inducing molecules. overexpression counteracted antiatherosclerotic effect mediated Bach1-deletion Rosuvastatin upregulating microRNA let-7a vascular endothelium hyperlipidemic colocalized YAP, positively correlated genes, as well Conclusions: These data identify mechanosensor hemodynamic reveal BACH1-YAP transcriptional network is essential inflammation atherogenesis. shows potential novel therapeutic target atherosclerosis.

Язык: Английский

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Mechanisms of diabetic foot ulceration: A review

Journal of Diabetes, Год журнала: 2023, Номер 15(4), С. 299 - 312

Опубликована: Март 9, 2023

Diabetic foot ulcers (DFUs) are associated with complex pathogenic factors and considered a serious complication of diabetes. The potential mechanisms underlying DFUs have been increasingly investigated. Previous studies focused on the three aspects diabetic peripheral vascular disease, neuropathy, wound infections. With advances in technology, researchers gradually conducting using immune cells, endothelial keratinocytes, fibroblasts, as they involved healing. It has reported that upregulation or downregulation molecular signaling pathways is essential for healing DFUs. recent increase awareness epigenetics, its regulatory role become much sought-after trend treatment This review focuses four pathogenesis DFUs: physiological pathological mechanisms, cellular pathway epigenetics. Given challenge DFUs, we hopeful our will provide new ideas peers.糖尿病足溃疡(DFUs)与复杂的病理因素有关，被认为是糖尿病的严重并发症。目前，潜在的DFUs机制已经越来越受到研究关注。以往的研究主要集中在糖尿病周围血管疾病、神经病变和创伤感染三个方面。随着技术的进步，研究人员逐渐开始使用免疫细胞、内皮细胞、角质细胞和成纤维细胞进行研究，因为它们参与了创伤愈合过程。报道称，分子信号通路的上调或下调对DFUs的愈合至关重要。随着对表观遗传学认识的增强，它在创伤愈合中的调控作用成为治疗DFUs的热门趋势。本综述关注DFUs发病机制涉及的四个方面:生理和病理机制、细胞机制、分子信号通路机制和表观遗传学。鉴于DFUs治疗的挑战，我们希望本综述能为同行提供新思路。.

Язык: Английский

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