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1.
Int J Colorectal Dis ; 39(1): 84, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829434

RESUMO

OBJECTIVES: Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic factors. This study aims to assess the feasibility of using body composition and pathological features to predict LNM in early stage colorectal cancer (eCRC) patients. METHODS: A total of 192 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in the study. The cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the L3 vertebral body level in CT scans were measured using Image J software. Logistic regression analysis were conducted to identify the risk factors for LNM. The predictive accuracy and discriminative ability of the indicators were evaluated using receiver operating characteristic (ROC) curves. Delong test was applied to compare area under different ROC curves. RESULTS: LNM was observed in 32 out of 192 (16.7%) patients with eCRC. Multivariate analysis revealed that the ratio of skeletal muscle area to visceral fat area (SMA/VFA) (OR = 0.021, p = 0.007) and pathological indicators of vascular invasion (OR = 4.074, p = 0.020) were independent risk factors for LNM in eCRC patients. The AUROC for SMA/VFA was determined to be 0.740 (p < 0.001), while for vascular invasion, it was 0.641 (p = 0.012). Integrating both factors into a proposed predictive model resulted in an AUROC of 0.789 (p < 0.001), indicating a substantial improvement in predictive performance compared to relying on a single pathological indicator. CONCLUSION: The combination of the SMA/VFA ratio and vascular invasion provides better prediction of LNM in eCRC.


Assuntos
Composição Corporal , Neoplasias Colorretais , Metástase Linfática , Invasividade Neoplásica , Curva ROC , Humanos , Masculino , Feminino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X , Fatores de Risco , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Adulto , Estudos Retrospectivos , Análise Multivariada , Músculo Esquelético/patologia , Músculo Esquelético/diagnóstico por imagem , Vasos Sanguíneos/patologia , Vasos Sanguíneos/diagnóstico por imagem
2.
Environ Health Perspect ; 132(5): 57001, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701112

RESUMO

BACKGROUND: Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay. OBJECTIVES: We aimed to develop an automated morphometric approach for the vascular profile and assess the vascular morphology of health-concerning environmental chemicals. METHODS: High-resolution images of the entire vasculature in Tg(fli1a:eGFP) zebrafish were collected using a high-content imaging platform. We established a deep learning-based quantitative framework, ECA-ResXUnet, combined with MATLAB to segment the vascular networks and extract features. Vessel scores based on the rates of morphological changes were calculated to rank vascular toxicity. Potential biomarkers were identified by vessel-endothelium-gene-disease integrative analysis. RESULTS: Whole-trunk blood vessels and the cerebral vasculature in larvae exposed to 150 representative chemicals were automatically segmented as comparable to human-level accuracy, with sensitivity and specificity of 95.56% and 95.81%, respectively. Chemical treatments led to heterogeneous vascular patterns manifested by 31 architecture indexes, and the common cardinal vein (CCV) was the most affected vessel. The antipsychotic medicine haloperidol, flame retardant 2,2-bis(chloromethyl)trimethylenebis[bis(2-chloroethyl) phosphate], and tert-butylphenyl diphenyl phosphate ranked as the top three in vessel scores. Pesticides accounted for the largest group, with a vessel score of ≥1, characterized by a remarkable inhibition of subintestinal venous plexus and delayed development of CCV. Multiple-concentration evaluation of nine per- and polyfluoroalkyl substances (PFAS) indicated a low-concentration effect on vascular impairment and a positive association between carbon chain length and benchmark concentration. Target vessel-directed single-cell RNA sequencing of fli1a+ cells from larvae treated with λ-cyhalothrin, perfluorohexanesulfonic acid, or benzylbutyl phthalate, along with vessel-endothelium-gene-disease integrative analysis, uncovered potential associations with vascular disorders and identified biomarker candidates. DISCUSSION: This study provides a novel paradigm for phenotype-driven screenings of vascular-disrupting chemicals by converging morphological and transcriptomic profiles at a high-resolution level, serving as a powerful tool for large-scale toxicity tests. Our approach and the high-quality morphometric data facilitate the precise evaluation of vascular effects caused by environmental chemicals. https://doi.org/10.1289/EHP13214.


Assuntos
Peixe-Zebra , Animais , Poluentes Ambientais/toxicidade , Vasos Sanguíneos/efeitos dos fármacos
3.
Med Eng Phys ; 127: 104166, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692765

RESUMO

A profound investigation of the interaction mechanics between blood vessels and guidewires is necessary to achieve safe intervention. An interactive force model between guidewires and blood vessels is established based on cardiovascular fluid dynamics theory and contact mechanics, considering two intervention phases (straight intervention and contact intervention at a corner named "J-vessel"). The contributing factors of the force model, including intervention conditions, guidewire characteristics, and intravascular environment, are analyzed. A series of experiments were performed to validate the availability of the interactive force model and explore the effects of influential factors on intervention force. The intervention force data were collected using a 2-DOF mechanical testing system instrumented with a force sensor. The guidewire diameter and material were found to significantly impact the intervention force. Additionally, the intervention force was influenced by factors such as blood viscosity, blood vessel wall thickness, blood flow velocity, as well as the interventional velocity and interventional mode. The experiment of the intervention in a coronary artery physical vascular model confirms the practicality validation of the predicted force model and can provide an optimized interventional strategy for vascular interventional surgery. The enhanced intervention strategy has resulted in a considerable reduction of approximately 21.97 % in the force exerted on blood vessels, effectively minimizing the potential for complications associated with the interventional surgery.


Assuntos
Fenômenos Mecânicos , Vasos Sanguíneos/fisiologia , Modelos Cardiovasculares , Hidrodinâmica , Humanos , Fenômenos Biomecânicos , Modelos Biológicos , Vasos Coronários/fisiologia
4.
Sci Rep ; 14(1): 10588, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719919

RESUMO

Solitary wave solutions are of great interest to bio-mathematicians and other scientists because they provide a basic description of nonlinear phenomena with many practical applications. They provide a strong foundation for the development of novel biological and medical models and therapies because of their remarkable behavior and persistence. They have the potential to improve our comprehension of intricate biological systems and help us create novel therapeutic approaches, which is something that researchers are actively investigating. In this study, solitary wave solutions of the nonlinear Murray equation will be discovered using a modified extended direct algebraic method. These solutions represent a uniform variation in blood vessel shape and diameter that can be used to stimulate blood flow in patients with cardiovascular disease. These solutions are newly in the literature, and give researchers an important tool for grasping complex biological systems. To see how the solitary wave solutions behave, graphs are displayed using Matlab.


Assuntos
Dinâmica não Linear , Humanos , Modelos Cardiovasculares , Vasos Sanguíneos/fisiologia , Velocidade do Fluxo Sanguíneo , Algoritmos
5.
Biomed Phys Eng Express ; 10(4)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38806008

RESUMO

Atherosclerosis is a cardiovascular disease mainly caused by plaque deposition in blood vessels. Plaque comprises components such as thrombosis, fibrin, collagen, and lipid core. It plays an essential role in inducing rupture in a blood vessel. Generally, Plaque could be described as three kinds of elastic models: cellular Plaque, hypocellular Plaque, and calcified Plaque. The present study aimed to investigate the behavior of atherosclerotic plaque rupture according to different lipid cores using Fluid-Structure Interaction (FSI). The blood vessel was also varied with different thicknesses (0.05, 0.25, and 0.5 mm). In this study, FSI simulation with a cellular plaque model with various thicknesses was investigated to obtain information on plaque rupture. Results revealed that the blood vessel with Plaque having a lipid core represents higher stresses than those without a lipid core. Blood vessels' thin thickness, like a thin cap, results in more considerable than Von Mises stress. The result also suggests that even at low fracture stress, the risk of rupture due to platelet decomposition at the gap was more significant for cellular plaques.


Assuntos
Simulação por Computador , Doença da Artéria Coronariana , Modelos Cardiovasculares , Placa Aterosclerótica , Estresse Mecânico , Humanos , Placa Aterosclerótica/patologia , Doença da Artéria Coronariana/patologia , Vasos Sanguíneos/patologia , Lipídeos/química , Vasos Coronários/patologia , Elasticidade
6.
Curr Top Dev Biol ; 159: 344-370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38729681

RESUMO

The development of the vascular system is crucial in supporting the growth and health of all other organs in the body, and vascular system dysfunction is the major cause of human morbidity and mortality. This chapter discusses three successive processes that govern vascular system development, starting with the differentiation of the primitive vascular system in early embryonic development, followed by its remodeling into a functional circulatory system composed of arteries and veins, and its final maturation and acquisition of an organ specific semi-permeable barrier that controls nutrient uptake into tissues and hence controls organ physiology. Along these steps, endothelial cells forming the inner lining of all blood vessels acquire extensive heterogeneity in terms of gene expression patterns and function, that we are only beginning to understand. These advances contribute to overall knowledge of vascular biology and are predicted to unlock the unprecedented therapeutic potential of the endothelium as an avenue for treatment of diseases associated with dysfunctional vasculature.


Assuntos
Remodelação Vascular , Humanos , Animais , Vasos Sanguíneos/crescimento & desenvolvimento , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/embriologia , Neovascularização Fisiológica , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Diferenciação Celular , Desenvolvimento Embrionário , Endotélio Vascular/citologia
7.
Dev Biol ; 512: 26-34, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38705558

RESUMO

The signals that regulate peripheral blood vessel formation during development are still under investigation. The hormone leptin promotes blood vessel formation, adipose tissue establishment and expansion, tumor growth, and wound healing, but the underlying mechanisms for these actions are currently unknown. We investigated whether leptin promotes angiogenesis in the developing tail fin using embryonic transgenic xflk-1:GFP Xenopus laevis, which express a green fluorescent protein on vascular endothelial cells to mark blood vessels. We found that leptin protein is expressed in endothelial cells of developing blood vessels and that leptin treatment via injection increased phosphorylated STAT3 signaling, which is indicative of leptin activation of its receptor, in blood vessels of the larval tail fin. Leptin administration via media increased vessel length, branching, and reconnection with the cardinal vein, while decreased leptin signaling via immunoneutralization had an opposing effect on vessel development. We also observed disorganization of major vessels and microvessels of the tail fin and muscle when leptin signaling was decreased. Reduced leptin signaling lowered mRNA expression of cenpk, gpx1, and mmp9, markers for cell proliferation, antioxidation, and extracellular matrix remodeling/cell migration, respectively, in the developing tail, providing insight into three possible mechanisms underlying leptin's promotion of angiogenesis. Together these results illustrate that leptin levels are correlated with embryonic angiogenesis and that leptin coordinates multiple aspects of blood vessel growth and development, showing that leptin is an important morphogen during embryonic development.


Assuntos
Larva , Leptina , Neovascularização Fisiológica , Transdução de Sinais , Cauda , Xenopus laevis , Animais , Leptina/metabolismo , Cauda/irrigação sanguínea , Cauda/embriologia , Xenopus laevis/embriologia , Xenopus laevis/metabolismo , Larva/metabolismo , Vasos Sanguíneos/embriologia , Vasos Sanguíneos/metabolismo , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/genética , Animais Geneticamente Modificados , Fator de Transcrição STAT3/metabolismo , Embrião não Mamífero/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Regulação da Expressão Gênica no Desenvolvimento
9.
ACS Biomater Sci Eng ; 10(6): 3631-3654, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38815169

RESUMO

The transplantation of vascular grafts has emerged as a prevailing approach to address vascular disorders. However, the development of small-diameter vascular grafts is still in progress, as they serve in a more complicated mechanical environment than their counterparts with larger diameters. The biocompatibility and functional characteristics of small-diameter vascular grafts have been well developed; however, mismatch in mechanical properties between the vascular grafts and native arteries has not been accomplished, which might facilitate the long-term patency of small-diameter vascular grafts. From a point of view in mechanics, mimicking the nonlinear elastic mechanical behavior exhibited by natural blood vessels might be the state-of-the-art in designing vascular grafts. This review centers on elucidating the nonlinear elastic behavior of natural blood vessels and vascular grafts. The biological functionality and limitations associated with as-reported vascular grafts are meticulously reviewed and the future trajectory for fabricating biomimetic small-diameter grafts is discussed. This review might provide a different insight from the traditional design and fabrication of artificial vascular grafts.


Assuntos
Prótese Vascular , Vasos Sanguíneos , Elasticidade , Humanos , Vasos Sanguíneos/fisiologia , Animais , Materiais Biocompatíveis/química
10.
Biomed Mater ; 19(3)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38636492

RESUMO

Three-dimensional (3D) printing has emerged as a transformative technology for tissue engineering, enabling the production of structures that closely emulate the intricate architecture and mechanical properties of native biological tissues. However, the fabrication of complex microstructures with high accuracy using biocompatible, degradable thermoplastic elastomers poses significant technical obstacles. This is primarily due to the inherent soft-matter nature of such materials, which complicates real-time control of micro-squeezing, resulting in low fidelity or even failure. In this study, we employ Poly (L-lactide-co-ϵ-caprolactone) (PLCL) as a model material and introduce a novel framework for high-precision 3D printing based on the material plasticization process. This approach significantly enhances the dynamic responsiveness of the start-stop transition during printing, thereby reducing harmful errors by up to 93%. Leveraging this enhanced material, we have efficiently fabricated arrays of multi-branched vascular scaffolds that exhibit exceptional morphological fidelity and possess elastic moduli that faithfully approximate the physiological modulus spectrum of native blood vessels, ranging from 2.5 to 45 MPa. The methodology we propose for the compatibilization and modification of elastomeric materials addresses the challenge of real-time precision control, representing a significant advancement in the domain of melt polymer 3D printing. This innovation holds considerable promise for the creation of detailed multi-branch vascular scaffolds and other sophisticated organotypic structures critical to advancing tissue engineering and regenerative medicine.


Assuntos
Materiais Biocompatíveis , Elastômeros , Poliésteres , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Elastômeros/química , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Poliésteres/química , Materiais Biocompatíveis/química , Módulo de Elasticidade , Teste de Materiais , Humanos , Estresse Mecânico , Vasos Sanguíneos , Prótese Vascular
11.
J Dermatol Sci ; 114(2): 71-78, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38644095

RESUMO

BACKGROUND: Photoacoustic microscopy is expected to have clinical applications as a noninvasive and three-dimensional (3D) method of observing intradermal structures. OBJECTIVE: Investigate the applicability of a photoacoustic microscope equipped with two types of pulsed lasers that can simultaneously recognize hemoglobin and melanin. METHODS: 16 skin lesions including erythema, pigmented lesions, vitiligo and purpura, were analyzed to visualize 3D structure of melanin granule distribution and dermal blood vessels. 13 cases of livedo racemosa in cutaneous polyarteritis nodosa (cPN) were further analyzed to visualize the 3D structure of dermal blood vessels in detail. Vascular structure was also analyzed in the biopsy specimens obtained from tender indurated erythema of cPN by CD34 immunostaining. RESULTS: Hemoglobin-recognition signal clearly visualized the 3D structure of dermal blood vessels and melanin-recognition signal was consistently reduced in vitiligo. In livedo racemosa, the hemoglobin-recognition signal revealed a relatively thick and large reticular structure in the deeper layers that became denser and finer toward the upper layers. The numerical analysis revealed that the number of dermal blood vessels was 1.29-fold higher (p<0.05) in the deeper region of the lesion than that of normal skin. The CD34 immunohistochemical analysis in tender indurated erythema revealed an increased number of dermal vessels compared with normal skin in 88.9% (8/9) of the cases, suggesting that vascular network remodeling had occurred in cPN. CONCLUSION: The photoacoustic system has an advantage in noninvasively detecting dermal blood vessel structures that are difficult to recognize by two-dimensional histopathology specimen examination and is worth evaluating in various skin diseases.


Assuntos
Imageamento Tridimensional , Melaninas , Técnicas Fotoacústicas , Poliarterite Nodosa , Pele , Humanos , Técnicas Fotoacústicas/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Melaninas/análise , Adulto , Imageamento Tridimensional/métodos , Poliarterite Nodosa/diagnóstico por imagem , Poliarterite Nodosa/patologia , Poliarterite Nodosa/diagnóstico , Pele/patologia , Pele/diagnóstico por imagem , Pele/irrigação sanguínea , Idoso , Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/patologia , Hemoglobinas/análise , Biópsia , Adulto Jovem , Microscopia/métodos , Livedo Reticular/patologia , Livedo Reticular/diagnóstico por imagem , Antígenos CD34/análise , Antígenos CD34/metabolismo
12.
Int J Biol Macromol ; 268(Pt 2): 131685, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38641268

RESUMO

There is an increasing demand for small-diameter blood vessels. Currently, there is no clinically available small-diameter artificial vessel. Bacterial nanocellulose (BNC) has vast potential for applications in artificial blood vessels due to its good biocompatibility. At the same time, medical polyurethane (PU) is a highly elastic polymer material widely used in artificial blood vessels. This study reports a composite small-diameter BNC/PU conduit using a non-solvent-induced phase separation method with the highly hydrophilic BNC tube as the skeleton and the hydrophobic polycarbonate PU as the filling material. The results revealed that the compliance and mechanical matching of BNC/PU tubes were higher than BNC tubes; the axial/radial mechanical strength, burst pressure, and suture strength were significantly improved; the blood compatibility and cell compatibility were also excellent. The molecular and subcutaneous embedding tests showed that the composite tubes had lighter inflammatory reactions. The results of the animal substitution experiments showed that the BNC/PU tubes kept blood flow unobstructed without tissue proliferation after implantation in rats for 9 months. Thus, the BNC/PU small-diameter vascular prosthesis had the potential for long-term patency and acted as an ideal material for small-diameter vessels.


Assuntos
Prótese Vascular , Celulose , Poliuretanos , Poliuretanos/química , Celulose/química , Animais , Ratos , Teste de Materiais , Materiais Biocompatíveis/química , Elasticidade , Humanos , Masculino , Vasos Sanguíneos
13.
Biol Open ; 13(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38639409

RESUMO

Blood vessels serve as intermediate conduits for the extension of sympathetic axons towards target tissues, while also acting as crucial targets for their homeostatic processes encompassing the regulation of temperature, blood pressure, and oxygen availability. How sympathetic axons innervate not only blood vessels but also a wide array of target tissues is not clear. Here we show that in embryonic skin, after the establishment of co-branching between sensory nerves and blood vessels, sympathetic axons invade the skin alongside these sensory nerves and extend their branches towards these blood vessels covered by vascular smooth muscle cells (VSMCs). Our mosaic labeling technique for sympathetic axons shows that collateral branching predominantly mediates the innervation of VSMC-covered blood vessels by sympathetic axons. The expression of nerve growth factor (NGF), previously known to induce collateral axon branching in culture, can be detected in the vascular smooth muscle cell (VSMC)-covered blood vessels, as well as sensory nerves. Indeed, VSMC-specific Ngf knockout leads to a significant decrease of collateral branching of sympathetic axons innervating VSMC-covered blood vessels. These data suggest that VSMC-derived NGF serves as an inductive signal for collateral branching of sympathetic axons innervating blood vessels in the embryonic skin.


Assuntos
Músculo Liso Vascular , Fator de Crescimento Neural , Pele , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/inervação , Fator de Crescimento Neural/metabolismo , Camundongos , Pele/inervação , Pele/irrigação sanguínea , Pele/metabolismo , Miócitos de Músculo Liso/metabolismo , Axônios/metabolismo , Axônios/fisiologia , Vasos Sanguíneos/embriologia , Vasos Sanguíneos/inervação , Vasos Sanguíneos/metabolismo , Sistema Nervoso Simpático/embriologia , Sistema Nervoso Simpático/fisiologia , Sistema Nervoso Simpático/metabolismo , Camundongos Knockout
14.
Biomater Adv ; 161: 213867, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38669824

RESUMO

Graphene and graphene oxide (GO), due to their unique chemical and physical properties, possess biochemical characteristics that can trigger intercellular signals promoting tissue regeneration. Clinical applications of thin GO-derived sheets have inspired the development of various tissue regeneration and repair approaches. In this study, we demonstrate that ultrathin sheets of plasma-functionalized and reduced GO, with the oxygen content ranging from 3.2 % to 22 % and the nitrogen content from 0 % to 8.3 %, retain their essential mechanical and molecular integrity, and exhibit robust potential for regenerating bone tissue and blood vessels across multiple cellular and animal models. Initially, we observed the growth of blood vessels and bone tissue in vitro using these functionalized GO sheets on human adipose-derived mesenchymal stem cells and umbilical vein endothelial cells. Remarkably, our study indicates a 2.5-fold increase in mineralization and two-fold increase in tubule formation even in media lacking osteogenic and angiogenic supplements. Subsequently, we observed the initiation, conduction, and formation of bone and blood vessels in a rat tibial osteotomy model, evident from a marked 4-fold increase in the volume of low radio-opacity bone tissue and a significant elevation in connectivity density, all without the use of stem cells or growth factors. Finally, we validated these findings in a mouse critical-size calvarial defect model (33 % higher healing rate) and a rat skin lesion model (up to 2.5-fold increase in the number of blood vessels, and 35 % increase in blood vessels diameter). This study elucidates the pro-osteogenic and pro-angiogenic properties of both pristine and plasma-treated GO ultrathin films. These properties suggest their significant potential for clinical applications, and as valuable biomaterials for investigating fundamental aspects of bone and blood vessel regeneration.


Assuntos
Regeneração Óssea , Grafite , Células Endoteliais da Veia Umbilical Humana , Células-Tronco Mesenquimais , Animais , Grafite/química , Humanos , Ratos , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Camundongos , Vasos Sanguíneos , Ratos Sprague-Dawley , Osso e Ossos/irrigação sanguínea , Osso e Ossos/efeitos dos fármacos , Gases em Plasma/farmacologia , Gases em Plasma/química , Tíbia/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Engenharia Tecidual/métodos
15.
Int J Biol Macromol ; 267(Pt 1): 131369, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580026

RESUMO

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (-25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels.


Assuntos
Antioxidantes , Quitosana , Nanopartículas em Multicamadas , Ácido Poliglutâmico , Polissacarídeos , Quercetina , Peixe-Zebra , Zeína , Animais , Humanos , Masculino , Ratos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Antioxidantes/química , Vasos Sanguíneos/efeitos dos fármacos , Quitosana/química , Portadores de Fármacos/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/patologia , Nanopartículas em Multicamadas/química , Peso Molecular , Tamanho da Partícula , Ácido Poliglutâmico/química , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Quercetina/farmacologia , Quercetina/química , Zeína/química
16.
Pharmacol Res ; 203: 107140, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513826

RESUMO

The understanding of the function of perivascular adipose tissue (PVAT) in vascular aging has significantly changed due to the increasing amount of information regarding its biology. Adipose tissue surrounding blood vessels is increasingly recognized as a key regulator of vascular disorders. It has significant endocrine and paracrine effects on the vasculature and is mediated by the production of a variety of bioactive chemicals. It also participates in a number of pathological regulatory processes, including oxidative stress, immunological inflammation, lipid metabolism, vasoconstriction, and dilation. Mechanisms of homeostasis and interactions between cells at the local level tightly regulate the function and secretory repertoire of PVAT, which can become dysregulated during vascular aging. The PVAT secretion group changes from being reducing inflammation and lowering cholesterol to increasing inflammation and increasing cholesterol in response to systemic or local inflammation and insulin resistance. In addition, the interaction between the PVAT and the vasculature is reciprocal, and the biological processes of PVAT are directly influenced by the pertinent indicators of vascular aging. The architectural and biological traits of PVAT, the molecular mechanism of crosstalk between PVAT and vascular aging, and the clinical correlation of vascular age-related disorders are all summarized in this review. In addition, this paper aims to elucidate and evaluate the potential benefits of therapeutically targeting PVAT in the context of mitigating vascular aging. Furthermore, it will discuss the latest advancements in technology used for targeting PVAT.


Assuntos
Tecido Adiposo , Envelhecimento , Vasos Sanguíneos , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Animais , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/metabolismo , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologia
17.
Int J Numer Method Biomed Eng ; 40(5): e3811, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38468441

RESUMO

The dialysis catheter indwelling in human bodies has a high risk of inducing thrombus and stenosis. Biomechanical research showed that such physiological complications are triggered by the wall shear stress of the vascular vessel. This study aimed to assess the impact of CVC implantation on central venous haemodynamics and the potential alterations in the haemodynamic environment related to thrombus development. The SVC structure was built from the images from computed tomography. The blood flow was calculated using the Carreau model, and the fluid domain was determined by CFD. The vascular wall and the CVC were computed using FEA. The elastic interaction between the vessel wall and the flow field was considered using FSI simulation. With consideration of the effect of coupling, it was shown that the catheter vibrated in the vascular systems due to the periodic variation of blood pressure, with an amplitude of up to 10% of the vessel width. Spiral flow was observed along the catheter after CVC indwelling, and recirculation flow appeared near the catheter tip. High OSI and WSS regions occurred at the catheter tip and the vascular junction. The arterial lumen tip had a larger effect on the WSS and OSI values on the vascular wall. Considering FSI simulation, the movement of the catheter inside the blood flow was simulated in the deformable vessel. After CVC indwelling, spiral flow and recirculation flow were observed near the regions with high WSS and OSI values.


Assuntos
Modelos Cardiovasculares , Diálise Renal , Humanos , Hemodinâmica/fisiologia , Elasticidade , Estresse Mecânico , Simulação por Computador , Velocidade do Fluxo Sanguíneo/fisiologia , Vasos Sanguíneos/fisiologia
18.
Comput Med Imaging Graph ; 114: 102364, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38432060

RESUMO

Vascular landmark detection plays an important role in medical analysis and clinical treatment. However, due to the complex topology and similar local appearance around landmarks, the popular heatmap regression based methods always suffer from the landmark confusion problem. Vascular landmarks are connected by vascular segments and have special spatial correlations, which can be utilized for performance improvement. In this paper, we propose a multi-task global optimization-based framework for accurate and automatic vascular landmark detection. A multi-task deep learning network is exploited to accomplish landmark heatmap regression, vascular semantic segmentation, and orientation field regression simultaneously. The two auxiliary objectives are highly correlated with the heatmap regression task and help the network incorporate the structural prior knowledge. During inference, instead of performing a max-voting strategy, we propose a global optimization-based post-processing method for final landmark decision. The spatial relationships between neighboring landmarks are utilized explicitly to tackle the landmark confusion problem. We evaluated our method on a cerebral MRA dataset with 564 volumes, a cerebral CTA dataset with 510 volumes, and an aorta CTA dataset with 50 volumes. The experiments demonstrate that the proposed method is effective for vascular landmark localization and achieves state-of-the-art performance.


Assuntos
Pontos de Referência Anatômicos , Vasos Sanguíneos , Análise de Regressão , Vasos Sanguíneos/anatomia & histologia , Humanos
19.
Nature ; 627(8005): 839-846, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38509363

RESUMO

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.


Assuntos
Hematopoese , Células-Tronco Hematopoéticas , Estresse Fisiológico , Animais , Feminino , Masculino , Camundongos , Envelhecimento/fisiologia , Infecções Bacterianas/patologia , Infecções Bacterianas/fisiopatologia , Vasos Sanguíneos/citologia , Linhagem da Célula , Eritropoese , Fator Estimulador de Colônias de Granulócitos/metabolismo , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Hemorragia/patologia , Hemorragia/fisiopatologia , Linfopoese , Megacariócitos/citologia , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismo , Mielopoese , Crânio/irrigação sanguínea , Crânio/patologia , Crânio/fisiopatologia , Esterno/irrigação sanguínea , Esterno/citologia , Esterno/metabolismo , Estresse Fisiológico/fisiologia , Tíbia/irrigação sanguínea , Tíbia/citologia , Tíbia/metabolismo
20.
Adv Healthc Mater ; 13(13): e2303320, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38354361

RESUMO

Volumetric muscle loss (VML), a severe muscle tissue loss from trauma or surgery, results in scarring, limited regeneration, and significant fibrosis, leading to lasting reductions in muscle mass and function. A promising approach for VML recovery involves restoring vascular and neural networks at the injury site, a process not extensively studied yet. Collagen hydrogels have been investigated as scaffolds for blood vessel formation due to their biocompatibility, but reconstructing blood vessels and guiding innervation at the injury site is still difficult. In this study, collagen hydrogels with varied densities of vessel-forming cells are implanted subcutaneously in mice, generating pre-vascularized hydrogels with diverse vessel densities (0-145 numbers/mm2) within a week. These hydrogels, after being transplanted into muscle injury sites, are assessed for muscle repair capabilities. Results showed that hydrogels with high microvessel densities, filling the wound area, effectively reconnected with host vasculature and neural networks, promoting neovascularization and muscle integration, and addressing about 63% of the VML.


Assuntos
Hidrogéis , Neovascularização Fisiológica , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Alicerces Teciduais/química , Colágeno/química , Colágeno/farmacologia , Vasos Sanguíneos
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