TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 5, 2023

Abstract Transient receptor potential (TRP) channels are sensors for a variety of cellular and environmental signals. Mammals express total 28 different TRP channel proteins, which can be divided into seven subfamilies based on amino acid sequence homology: TRPA (Ankyrin), TRPC (Canonical), TRPM (Melastatin), TRPML (Mucolipin), TRPN (NO-mechano-potential, NOMP), TRPP (Polycystin), TRPV (Vanilloid). They class ion found in numerous tissues cell types permeable to wide range cations such as Ca 2+ , Mg Na + K others. responsible various sensory responses including heat, cold, pain, stress, vision taste activated by number stimuli. Their predominantly location the surface, their interaction with physiological signaling pathways, unique crystal structure make TRPs attractive drug targets implicate them treatment diseases. Here, we review history discovery, summarize structures functions family, highlight current understanding role pathogenesis human disease. Most importantly, describe channel-related therapeutic interventions diseases limitations targeting clinical applications.

Язык: Английский

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Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies

Cell Death and Disease, Год журнала: 2023, Номер 14(2)

Опубликована: Фев. 11, 2023

Abstract Copper is a vital mineral, and an optimal amount of copper required to support normal physiologic processes in various systems, including the cardiovascular system. Over past few decades, copper-induced cell death, named cuproptosis, has become increasingly recognized as important process mediating pathogenesis progression disease (CVD), atherosclerosis, stroke, ischemia-reperfusion injury, heart failure. Therefore, in-depth understanding regulatory mechanisms cuproptosis CVD may be useful for improving management. Here, we review relationship between homeostasis cuproptosis-related pathways CVD, well therapeutic strategies addressing death CVD.

Язык: Английский

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Multifunctional nanoparticle-mediated combining therapy for human diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 1, 2024

Abstract Combining existing drug therapy is essential in developing new therapeutic agents disease prevention and treatment. In preclinical investigations, combined effect of certain known drugs has been well established treating extensive human diseases. Attributed to synergistic effects by targeting various pathways advantages, such as reduced administration dose, decreased toxicity, alleviated resistance, combinatorial treatment now being pursued delivering combat major clinical illnesses, cancer, atherosclerosis, pulmonary hypertension, myocarditis, rheumatoid arthritis, inflammatory bowel disease, metabolic disorders neurodegenerative Combinatorial involves combining or co-delivering two more for a specific disease. Nanoparticle (NP)-mediated delivery systems, i.e., liposomal NPs, polymeric NPs nanocrystals, are great interest wide range due targeted delivery, extended release, higher stability avoid rapid clearance at infected areas. This review summarizes targets diseases, clinically approved combinations the development multifunctional emphasizes strategies based on severe Ultimately, we discuss challenging NP-codelivery translation provide potential approaches address limitations. offers comprehensive overview recent cutting-edge NP-mediated combination

Язык: Английский

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Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7910 - 7910

Опубликована: Апрель 26, 2023

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from general pathology perspective, particularly with regard atherogenesis patterns in context both canonical and non-classical inflammation types. In review, we analyze various typical phenomena outcomes cellular pro-inflammatory stress atherosclerosis, as well role endothelial dysfunction local systemic manifestations low-grade inflammation. We also present features immune development productive stable unstable plaques, along their similarities differences compared There are numerous factors that act inducers inflammatory process including vascular endothelium aging, metabolic dysfunctions, autoimmune, some cases, infectious damage factors. Life-critical complications such cardiogenic shock severe strokes, associated acute hyperinflammation. Additionally, critical atherosclerotic ischemia lower extremities induces paracoagulation chronic Conversely, sepsis, other conditions, diseases contribute atherogenesis. summary, can be characterized an independent form inflammation, sharing but having fundamental variants (classic vasculitis).

Язык: Английский

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Cardiovascular disease and cancer: shared risk factors and mechanisms

Nature Reviews Cardiology, Год журнала: 2024, Номер 21(9), С. 617 - 631

Опубликована: Апрель 10, 2024

Язык: Английский

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Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing

Cell Reports Medicine, Год журнала: 2023, Номер 4(8), С. 101129 - 101129

Опубликована: Июль 21, 2023

Moderate inflammation is essential for standard wound healing. In pathological conditions, such as diabetes, protracted and refractory wounds are associated with excessive inflammation, manifested by persistent proinflammatory macrophage states. However, the mechanisms still unclear. Herein, we perform a metabolomic profile find significant phenylpyruvate accumulation in diabetic foot ulcers. Increased impairs healing augments inflammatory responses, whereas reducing via dietary phenylalanine restriction relieves uncontrolled benefits wounds. Mechanistically, ingested into macrophages scavenger receptor CD36-dependent manner, binds to PPT1, inhibits depalmitoylase activity, thus increasing palmitoylation of NLRP3 protein. found enhance protein stability, decrease lysosome degradation, promote inflammasome activation release factors, interleukin (IL)-1β, finally triggering phenotype. Our study suggests potential strategy targeting prevent

Язык: Английский

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Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 15, 2023

Bile acids (BAs) as cholesterol-derived molecules play an essential role in some physiological processes such nutrient absorption, glucose homeostasis and regulation of energy expenditure. They are synthesized the liver primary BAs cholic acid (CA), chenodeoxycholic (CDCA) conjugated forms. A variety secondary deoxycholic (DCA) lithocholic (LCA) their derivatives is intestine through involvement various microorganisms. In addition to functions, metabolites also involved differentiation functions innate adaptive immune cells macrophages (Macs), dendritic (DCs), myeloid derived suppressive (MDSCs), regulatory T (Treg), Breg cells, helper (Th)17 CD4 Th1 Th2 CD8 B NKT cells. Dysregulation affects development diseases inflammatory bowel diseases. We here summarize recent advances how maintain gut systemic homeostasis, including metabolism derivatives, function effects on immune-associated disorders.

Язык: Английский

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Design of a Multifunctional Nanozyme for Resolving the Proinflammatory Plaque Microenvironment and Attenuating Atherosclerosis

ACS Nano, Год журнала: 2023, Номер 17(15), С. 14555 - 14571

Опубликована: Июнь 23, 2023

Persistent inflammation within atherosclerotic plaques is a crucial factor contributing to plaque vulnerability and rupture. It has become increasingly evident that the proinflammatory microenvironment of plaque, characterized by heightened monocyte recruitment, oxidative stress, impaired clearance apoptotic cells, plays significant role in perpetuating impeding its resolution. Consequently, targeting eliminating these features have emerged as promising therapeutic approach restore resolution mitigate progression atherosclerosis. While recent advancements nanotherapeutics demonstrated results individual characteristics, development an effective strategy capable simultaneously addressing multiple remains challenge. In this study, we developed multifunctional nanozyme based on Prussian blue, termed PBNZ@PP-Man, target eliminate various factors microenvironment. Through systematic investigations, elucidated antiatherosclerotic mechanisms PBNZ@PP-Man. Our demonstrate PBNZ@PP-Man possesses ability accumulate effectively factors, leading Specifically, suppresses scavenges reactive oxygen species, enhances efferocytosis. Notably, exhibits much stronger efficacy resolve attenuate atherosclerosis comparison merely eliminates one single risky plaque. significantly capabilities macrophages attenuates These collectively underscore importance modulating complementary for resolving

Язык: Английский

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Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

Advanced Materials, Год журнала: 2024, Номер 36(18)

Опубликована: Янв. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Язык: Английский

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Vascular remodelling in cardiovascular diseases: hypertension, oxidation, and inflammation

Clinical Science, Год журнала: 2024, Номер 138(13), С. 817 - 850

Опубликована: Июнь 26, 2024

Abstract Optimal vascular structure and function are essential for maintaining the physiological functions of cardiovascular system. Vascular remodelling involves changes in vessel structure, including its size, shape, cellular molecular composition. These result from multiple risk factors may be compensatory adaptations to sustain blood function. They occur diverse pathologies, hypertension heart failure atherosclerosis. Dynamic endothelium, fibroblasts, smooth muscle cells, pericytes or other wall cells underlie remodelling. In addition, immune macrophages lymphocytes, infiltrate vessels initiate inflammatory signalling. contribute a dynamic interplay between cell proliferation, apoptosis, migration, inflammation, extracellular matrix reorganisation, all critical mechanisms Molecular pathways underlying these processes include growth (e.g., endothelial factor platelet-derived factor), cytokines interleukin-1β tumour necrosis factor-α), reactive oxygen species, signalling pathways, such as Rho/ROCK, MAPK, TGF-β/Smad, related nitric oxide superoxide biology. MicroRNAs long noncoding RNAs crucial epigenetic regulators gene expression We evaluate potential therapeutic targeting clinical translational perspective. summary, remodelling, coordinated modification function, is disease pathology.

Язык: Английский

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