Microcirculation最新文献_第9页

Lentiviral overexpression of VEGFC in transplanted MSCs leads to resolution of swelling in a mouse tail lymphedema model 慢病毒在移植骨髓间充质干细胞中过表达VEGFC导致小鼠尾部淋巴水肿模型肿胀消退

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-11-12 DOI: 10.1111/micc.12792

Eleftheria Michalaki, Josephine M. Rudd, Lauren Liebman, Rahul Wadhwani, Levi B. Wood, Nick J. Willett, J. Brandon Dixon

Background

Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Despite the various physical therapy and surgical options available, most treatments are palliative and fail to address the underlying lymphatic vascular insufficiency driving lymphedema progression. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases with a wide range of therapeutic effects that reduce inflammation, fibrosis, and oxidative stress, while promoting lymphatic vessel (LV) regeneration. Specifically, stem cell transplantation is suggested to promote LV restoration, rebuild lymphatic circulation, and thus potentially be utilized towards an effective lymphedema treatment. In addition to stem cells, studies have proposed the administration of vascular endothelial growth factor C (VEGFC) to promote lymphangiogenesis and decrease swelling in lymphedema.

Aims

Here, we seek to combine the benefits of stem cell therapy, which provides a cellular therapeutic approach that can respond to the tissue environment, and VEGFC administration to restore lymphatic drainage.

Materials & Methods

Specifically, we engineered mesenchymal stem cells (MSCs) to overexpress VEGFC using a lentiviral vector (hVEGFC MSC) and investigated their therapeutic efficacy in improving LV function and tissue swelling using near infrared (NIR) imaging, and lymphatic regeneration in a single LV ligation mouse tail lymphedema model.

Results

First, we showed that overexpression of VEGFC using lentiviral transduction led to an increase in VEGFC protein synthesis in vitro. Then, we demonstrated hVEGFC MSC administration post-injury significantly increased the lymphatic contraction frequency 14-, 21-, and 28-days post-surgery compared to the control animals (MSC administration) in vivo, while also reducing tail swelling 28-days post-surgery compared to controls.

Conclusion

Our results suggest a therapeutic potential of hVEGFC MSC in alleviating the lymphatic dysfunction observed during lymphedema progression after secondary injury and could provide a promising approach to enhancing autologous cell therapy for treating lymphedema.

背景淋巴系统在受伤、疾病或癌症治疗后的功能障碍可导致淋巴水肿，这是一种无法治愈的衰弱性疾病。尽管有各种物理治疗和手术选择，但大多数治疗都是姑息性的，无法解决导致淋巴水肿进展的潜在淋巴管功能不全。干细胞疗法为治疗各种慢性疾病提供了一种有前景的替代方案，具有广泛的治疗效果，可以减少炎症、纤维化和氧化应激，同时促进淋巴管（LV）再生。具体而言，干细胞移植可促进左心室恢复，重建淋巴循环，从而有可能用于有效的淋巴水肿治疗。除了干细胞外，研究还提出了血管内皮生长因子C（VEGFC）的给药，以促进淋巴管生成并减少淋巴水肿中的肿胀。目的在这里，我们寻求将干细胞治疗和VEGFC给药的好处结合起来，干细胞治疗提供了一种可以对组织环境做出反应的细胞治疗方法，以恢复淋巴引流。材料&；方法具体而言，我们使用慢病毒载体（hVEGFC-MSC）改造间充质干细胞（MSC）以过表达VEGFC，并使用近红外（NIR）成像研究其在改善左心室功能和组织肿胀方面的治疗效果，以及在单LV结扎小鼠尾部淋巴水肿模型中的淋巴再生。结果首先，我们发现使用慢病毒转导的VEGFC过表达导致体外VEGFC蛋白合成增加。然后，我们证明，与体内对照动物（MSC给药）相比，损伤后给予hVEGFC MSC显著增加了手术后14、21和28天的淋巴收缩频率，同时与对照相比，也减少了手术后28天的尾部肿胀。结论hVEGFC-MSC在减轻继发性损伤后淋巴水肿进展过程中观察到的淋巴功能障碍方面具有治疗潜力，可为加强自体细胞治疗淋巴水肿提供一种有前景的方法。

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引用次数: 1

GATA2 regulates blood/lymph separation in a platelet-dependent and lymphovenous valve-independent manner GATA2以血小板依赖和淋巴静脉瓣膜不依赖的方式调节血液/淋巴分离

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-10-05 DOI: 10.1111/micc.12787

Md. Riaj Mahamud, Xin Geng, Lijuan Chen, Zoheb Ahmed, Yenchun Ho, R. Sathish Srinivasan

Introduction

Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids and return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular valves LVVs prevent the backflow of blood into the lymphatic vessels. In addition to LVVs, platelets are necessary to prevent the entry of blood into the lymphatic vessels. Platelet thrombi are observed at LVVs suggesting that LVVs and platelets function in synergy to regulate blood/lymphatic separation.

Objectives

The primary objective of this work is to determine whether platelets can regulate blood/lymph separation independently of LVVs.

Methods

The transcription factor GATA2 is necessary for the development of both LVVs and hematopoietic stem cells. Using various endothelial- and hematopoietic cell expressed Cre-lines, we conditionally deleted Gata2. We hypothesized that this strategy would identify the tissue- and time-specific roles of GATA2 and reveal whether platelets and LVVs can independently regulate blood/lymph separation.

Results

Lymphatic vasculature-specific deletion of Gata2 results in the absence of LVVs without compromising blood/lymph separation. In contrast, deletion of GATA2 from both lymphatic vasculature and hematopoietic cells results in the absence of LVVs, reduced number of platelets and blood-filled lymphatic vasculature.

Conclusion

GATA2 promotes blood/lymph separation through platelets. Furthermore, LVVs are the only known sites of interaction between blood and lymphatic vessels. The fact that blood is able to enter the lymphatic vessels of mice lacking LVVs and platelets indicates that under these circumstances the lymphatic and blood vessels are connected at yet to be identified sites.

淋巴管收集间质液、免疫细胞和消化的脂质，并通过两对淋巴静脉瓣膜(LVVs)将这些体液送回血液。像其他心血管瓣膜一样，左心室防止血液回流到淋巴管。除了左心室外，血小板也是防止血液进入淋巴管所必需的。在左心室观察到血小板血栓，提示左心室和血小板协同作用调节血液/淋巴分离。这项工作的主要目的是确定血小板是否可以独立于lvv调节血液/淋巴分离。方法转录因子GATA2是LVVs和造血干细胞发育所必需的。使用多种内皮细胞和造血细胞表达的cre细胞系，我们有条件地删除了Gata2。我们假设这种策略可以确定GATA2的组织和时间特异性作用，并揭示血小板和lvv是否可以独立调节血液/淋巴分离。结果淋巴血管特异性缺失Gata2导致lvv缺失，但不影响血淋巴分离。相比之下，淋巴血管和造血细胞中GATA2的缺失导致lvv缺失，血小板数量减少，淋巴血管充血。结论GATA2通过血小板促进血淋巴分离。此外，左心室是唯一已知的血液和淋巴管相互作用的部位。血液能够进入缺乏lvv和血小板的小鼠的淋巴管这一事实表明，在这种情况下，淋巴管和血管在尚未确定的位置连接。

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引用次数: 1

RNA-seq profiling reveals different pathways between remodeled vessels and myocardium in hypertrophic cardiomyopathy RNA-seq分析揭示了肥厚性心肌病重构血管和心肌之间的不同途径

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-10-05 DOI: 10.1111/micc.12790

Annalinda Pisano, Loredana Le Pera, Raffaella Carletti, Bruna Cerbelli, Maria G. Pignataro, Angelina Pernazza, Fabrizio Ferre, Maria Lombardi, Davide Lazzeroni, Iacopo Olivotto, Ornella E. Rimoldi, Chiara Foglieni, Paolo G. Camici, Giulia d'Amati

Objective

Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM.

Methods

Interventricular septum myectomies from patients with obstructive HCM (n = 20) and donors' hearts (CTRL, discarded for technical reasons, n = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile.

Results

We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls.

Conclusions

We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level.

目的冠状动脉微血管功能障碍(CMD)是肥厚性心肌病(HCM)的关键病理生理特征，有助于心肌缺血，是患者不良结局的关键决定因素。其形态和功能变化的分子机制尚不清楚。本研究的目的是了解HCM微血管重构的相关分子途径。方法收集梗阻性HCM患者(n = 20)的室间隔肌瘤切除术和供体心脏(CTRL，因技术原因丢弃，n = 7)。重构的心内小动脉和心肌细胞通过激光捕获进行显微解剖，并使用下一代测序来描绘转录组谱。结果在心肌细胞中鉴定出720个特异性差异表达基因(deg)，在HCM重构小动脉中鉴定出1315个特异性差异表达基因(deg)。通过基因本体论和途径富集分析，我们在HCM患者和对照组中发现了重构小动脉和心肌细胞之间选择性改变的途径。在转录组水平上，我们证明了HCM患者和对照组中重构小动脉和心肌细胞之间存在不同的通路。

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引用次数: 1

Impact of Goreisan components on rat mesenteric collecting lymphatic vessel pumping 葛瑞山成分对大鼠肠系膜集淋巴管泵送的影响

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-09-28 DOI: 10.1111/micc.12788

Michiko Jo, Andrea N. Trujillo, Naotoshi Shibahara, Jerome W. Breslin

Background

Goreisan is a traditional herbal formulation with diuretic properties tested as a clinical therapeutic to alleviate lymphedema in Japan. The present study aimed to determine how Goreisan and its five different components affect lymphatic pump function.

Methods

Mesenteric collecting lymphatics were isolated from anesthetized Sprague–Dawley rats and mounted on resistance-matched glass micropipettes in a 37°C physiological salt solution bath for studies. Diameter was continuously measured to obtain the following lymphatic pump parameters: contraction frequency (CF), end diastolic diameter (EDD), and end systolic diameter (ESD), contraction amplitude (AMP), ejection fraction (EF), and fractional pump flow (FPF). Goreisan and each of its components (Cinnamomi Cortex, Atractylodis Rhizoma, Alismatis Rhizoma, Polyporus, and Poria) were applied to the bath at concentrations of 1–30 μg/mL.

Results

The results show that while Goreisan causes no significant changes to lymphatic pumping, Alismatis Rhizoma and Polyporus each significantly reduce CF and FPF. In addition, rats that received oral administration of Goreisan and Alismatis Rhizoma for 1 week had elevated expression of VEGFR-3 in their mesenteric collecting lymphatics.

Conclusions

Collectively, the results suggest that some components of Goreisan have a direct, rapid impact on lymphatic pumping. These findings provide new insights but also raise new questions about the therapeutic potential of Goreisan in patients with secondary lymphedema.

背景Goreisan是一种传统的草药配方，具有利尿的特性，在日本作为一种临床治疗方法来缓解淋巴水肿。本研究旨在确定Goreisan及其五种不同成分如何影响淋巴泵功能。方法分离麻醉后的sd大鼠肠系膜收集淋巴管，置于37℃生理盐液浴中进行实验研究。连续测量管径，获得以下淋巴泵参数:收缩频率(CF)、舒张末内径(EDD)、收缩末内径(ESD)、收缩幅值(AMP)、射血分数(EF)和泵流量分数(FPF)。Goreisan和它的每个组件(肉桂的皮层,Atractylodis根茎,Alismatis根茎,Polyporus,和云苓)被应用于浴浓度的外墙面μg / mL。结果丹参对大鼠淋巴泵无明显影响，泽泻和茯苓均能显著降低CF和FPF。此外，口服黄芩和泽泻1周的大鼠肠系膜集淋巴中VEGFR-3的表达升高。综上所述，结果表明高丽散的某些成分对淋巴泵送有直接、快速的影响。这些发现提供了新的见解，但也提出了关于Goreisan在继发性淋巴水肿患者中的治疗潜力的新问题。

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引用次数: 3

Irisin inhibits NLRP3 inflammasome activation in HG/HF incubated cardiac microvascular endothelial cells with H/R injury 鸢尾素抑制HG/HF培养H/R损伤心肌微血管内皮细胞NLRP3炎性体活化

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-09-24 DOI: 10.1111/micc.12786

Chao Xin, Jinglong Zhang, Ningbo Hao, Jianan Wang, Hui Liu, Hanwen Wei, Yong Wang, Chengzhu Wang, Shuo Wang, Chengrong Zheng, Zheng Zhang, Zhitao Jin

Purpose

NLRP3 inflammasome mediates myocardial ischemia/reperfusion (MI/R) injury and diabetic vascular endothelia dysfunction. However, the role of NLRP3 inflammasome in MI/R injury with diabetes has not been fully described. Irisin plays an important role in anti-inflammation and improves endothelial function in type 2 diabetes. The current study aimed to investigate the effect of irisin on regulating NLRP3 inflammasome activation in diabetic vascular endothelia dysfunction.

Methods

Cardiac microvascular endothelial cells (CMECs) were cultured and subjected to high glucose/high fat (HG/HF) receiving hypoxia/reoxygenation (H/R) with irisin incubation or not. Then, apoptosis, viability, migration, NO secretion, and inflammasome activation were examined.

Results

The hypoxic CMECs exhibited increased apoptosis, impaired viability, and migration, even decreased NO secretion and enhanced inflammasome activation. Moreover, irisin incubation decreased NLRP3 activation and attenuated cell injury in HG/HF cultured CMECs subjected to H/R injury, which was abolished by NLRP3 inflammasome activation. Meanwhile, NLRP3 inflammasome siRNA also attenuated H/R injury in CMECs under HG/HF condition.

Conclusion

The current study demonstrated for the first time that irisin inhibits NLRP3 inflammasome activation in CMECs as a novel mechanism in myocardial ischemia/reperfusion injury in diabetes.

目的NLRP3炎性体介导心肌缺血再灌注(MI/R)损伤和糖尿病血管内皮功能障碍。然而，NLRP3炎性体在糖尿病心肌梗死/再灌注损伤中的作用尚未得到充分描述。鸢尾素在2型糖尿病患者中具有抗炎和改善内皮功能的重要作用。本研究旨在探讨鸢尾素在糖尿病血管内皮功能障碍中调节NLRP3炎性体激活的作用。方法培养心脏微血管内皮细胞(CMECs)，进行高糖/高脂(HG/HF)缺氧/再氧化(H/R)，鸢尾素孵育或不孵育。然后检测细胞凋亡、活力、迁移、NO分泌和炎性体活化。结果缺氧cmec细胞凋亡增加，细胞活力和迁移能力受损，一氧化氮分泌减少，炎性体活化增强。此外，鸢尾素孵育可降低HG/HF培养的H/R损伤cmes的NLRP3激活并减轻细胞损伤，而NLRP3炎性体激活可消除H/R损伤。同时，NLRP3炎性小体siRNA也能减轻HG/HF条件下cmes的H/R损伤。结论本研究首次证实鸢尾素抑制CMECs NLRP3炎性体激活是糖尿病心肌缺血再灌注损伤的新机制。

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引用次数: 1

Visualizing the Microcirculation 可视化微循环

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-09-20 DOI: 10.1111/micc.12785

Janaka Senarathna, Arvind P. Pathak

Over the last century, scientific discoveries have revealed the critical role of the microcirculation in maintaining homeostasis and the etiology of diseases ranging from cancer to COVID-19. These advances have coincided with and even been made possible by the exponential progress in imaging and visualization techniques capable of characterizing the structural and functional diversity of the microcirculation. Consequently, this special issue (SI) showcases a broad selection of tools and methods for elucidating the role of the microcirculation in health and disease. In this exciting compendium of globally contributed articles, authors investigate in vitro and in vivo models, describe new imaging methods spanning from the endothelial cell to the whole organ scale, as well as analytical approaches focused on the microvascular and lymphatic systems. Also included are articles describing the use of ultrasound and photoacoustic imaging of the microcirculation in the clinical and preclinical realms. We believe this SI on "Visualizing the Microcirculation" contains something for everyone, from basic scientists to clinicians interested in the microcirculation.

引用次数: 0

Analysis and visualization methods for detecting functional activation using laser speckle contrast imaging 利用激光散斑对比成像检测功能激活的分析和可视化方法

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-09-07 DOI: 10.1111/micc.12783

Peng Hu, Bochao Niu, Hang Yang, Yang Xia, Donna Chen, Chun Meng, Ke Chen, Bharat Biswal

Background

Previous studies have used regional cerebral blood flow (CBF) hemodynamic response to measure brain activities. In this work, we use a laser speckle contrast imaging (LSCI) apparatus to sample the CBF activation in somatosensory cortex (S1BF) with repetitive whisker stimulation. Traditionally, the CBF activations were processed by depicting the change percentage above baseline; however, it is not clear how different methods influence the detection of activations.

Aims

Thus, in this work we investigate the influence of different methods to detect activations in LSCI.

Materials & Methods

First, principal component analysis (PCA) was performed to denoise the CBF signal. As the signal of the first principal component (PC1) showed the highest correlation with the S1BF CBF response curve, PC1 was used in the subsequent analyses. Then, we used fast Fourier transform (FFT) to evaluate the frequency properties of the LSCI images and the activation map was generated based on the amplitude of the central frequency. Furthermore, Pearson's correlation coefficient (C–C) analysis and a general linear model (GLM) were performed to estimate the S1BF activation based on the time series of PC1.

Results

We found that GLM performed better in identifying activation than C–C. Additionally, the activation maps generated by FFT were similar to those obtained by GLM. Particularly, the superficial vein and arterial vessels separated the activation region as segmented activated areas, and the regions with unresolved vessels showed a common activation for whisker stimulation.

Discussion and Conclusion

Our research analyzed the extent to which PCA can extract meaningful information from the signal and we compared the performance for detecting brain functional activation between different methods that rely on LSCI. This can be used as a reference for LSCI researchers on choosing the best method to estimate brain activation.

以往的研究使用脑区域血流动力学反应(CBF)来测量脑活动。在这项工作中，我们使用激光散斑对比成像(LSCI)设备对重复须刺激体感觉皮层(S1BF)的CBF激活进行了采样。传统上，CBF激活是通过描述高于基线的变化百分比来处理的;然而，目前尚不清楚不同的方法如何影响激活检测。因此，在这项工作中，我们研究了不同方法检测LSCI激活的影响。材料,方法首先采用主成分分析(PCA)对脑血流信号进行去噪处理。由于第一主成分(PC1)信号与S1BF CBF响应曲线的相关性最高，因此将PC1用于后续分析。然后，利用快速傅里叶变换(FFT)对LSCI图像的频率特性进行评估，并根据中心频率的幅值生成激活图;基于PC1的时间序列，采用Pearson相关系数(C-C)分析和一般线性模型(GLM)估计S1BF的激活。结果我们发现GLM比C-C更能识别激活。此外，FFT生成的激活图与GLM获得的激活图相似。特别是，浅表静脉和动脉血管将激活区分离为分段激活区，并且未解决的血管区域显示出对须刺激的共同激活。我们的研究分析了PCA从信号中提取有意义信息的程度，并比较了依赖LSCI的不同方法在检测脑功能激活方面的性能。这可以为LSCI研究者选择最佳的脑激活估计方法提供参考。

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引用次数: 2

Histone-stimulated platelet adhesion to mouse cremaster venules in vivo is dependent on von Willebrand factor 组蛋白刺激的血小板对小鼠小静脉的粘附依赖于血管性血友病因子

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-09-03 DOI: 10.1111/micc.12782

Justin A. Courson, Fong W. Lam, Kimberly W. Langlois, Rolando E. Rumbaut

Objective

Extracellular histones are known mediators of platelet activation, inflammation, and thrombosis. Von Willebrand Factor (vWF) and Toll-like receptor 4 (TLR4) have been implicated in pro-inflammatory and prothrombotic histone responses. The objective of this study was to assess the role of vWF and TLR4 on histone-induced platelet adhesion in vivo.

Methods

Intravital microscopy of the mouse cremaster microcirculation, in the presence of extracellular histones or saline control, was conducted in wild-type, vWF-deficient, and TLR4-deficient mice to assess histone-mediated platelet adhesion. Platelet counts following extracellular histone exposure were conducted. Platelets were isolated from vWF-deficient mice and littermates to assess the role of vWF on histone-induced platelet aggregation.

Results

Histones promoted platelet adhesion to cremaster venules in vivo in wild-type animals, as well as in TLR4-deficient mice to a comparable degree. Histones did not lead to increased platelet adhesion in vWF-deficient mice, in contrast to littermate controls. In all genotypes, histones resulted in thrombocytopenia. Histone-induced platelet aggregation ex vivo was similar in vWF-deficient mice and littermate controls.

Conclusions

Histone-induced platelet adhesion to microvessels in vivo is vWF-dependent and TLR4-independent. Platelet-derived vWF was not necessary for histone-induced platelet aggregation ex vivo. These data are consistent with the notion that endothelial vWF, rather than platelet vWF, mediates histone-induced platelet adhesion in vivo.

目的细胞外组蛋白是已知的血小板活化、炎症和血栓形成的介质。血管性血友病因子(vWF)和toll样受体4 (TLR4)参与促炎和血栓形成前组蛋白反应。本研究的目的是评估vWF和TLR4在组蛋白诱导的血小板粘附中的作用。方法对野生型、vwf缺陷型和tlr4缺陷型小鼠，在细胞外组蛋白存在或生理盐水对照下，进行小鼠乳糜微循环活体显微镜观察，以评估组蛋白介导的血小板粘附。细胞外组蛋白暴露后进行血小板计数。从vWF缺陷小鼠和窝仔中分离血小板，以评估vWF对组蛋白诱导的血小板聚集的作用。结果组蛋白在野生型动物和tlr4缺陷小鼠体内均可促进血小板粘附到小静脉。与对照组相比，组蛋白不会导致vwf缺陷小鼠血小板粘附增加。在所有基因型中，组蛋白导致血小板减少。组蛋白诱导的体外血小板聚集在vwf缺陷小鼠和同窝对照中相似。结论组蛋白诱导的血小板对微血管的粘附是vwf依赖性的，与tlr4无关。血小板来源的vWF对于组蛋白诱导的体外血小板聚集不是必需的。这些数据与内皮细胞vWF而不是血小板vWF在体内介导组蛋白诱导的血小板粘附的观点一致。

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引用次数: 0

Recent advancement of imaging strategies of the lymphatic system: Answer to the decades old questions 淋巴系统成像策略的最新进展:回答几十年的老问题

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-08-16 DOI: 10.1111/micc.12780

Priyanka Banerjee, Sukanya Roy, Sanjukta Chakraborty

The role of the lymphatic system in maintaining tissue homeostasis and a number of different pathophysiological conditions has been well established. The complex and delicate structure of the lymphatics along with the limitations of conventional imaging techniques make lymphatic imaging particularly difficult. Thus, in-depth high-resolution imaging of lymphatic system is key to understanding the progression of lymphatic diseases and cancer metastases and would greatly benefit clinical decisions. In recent years, the advancement of imaging technologies and development of new tracers suitable for clinical applications has enabled imaging of the lymphatic system in both clinical and pre-clinical settings. In this current review, we have highlighted the advantages and disadvantages of different modern techniques such as near infra-red spectroscopy (NIRS), positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI) and fluorescence optical imaging, that has significantly impacted research in this field and has led to in-depth insights into progression of pathological states. This review also highlights the use of current imaging technologies, and tracers specific for immune cell markers to identify and track the immune cells in the lymphatic system that would help understand disease progression and remission in immune therapy regimen.

淋巴系统在维持组织稳态和许多不同病理生理条件中的作用已经得到了很好的证实。淋巴管的复杂和精细结构以及传统成像技术的局限性使得淋巴管成像特别困难。因此，深入的高分辨率淋巴系统成像是了解淋巴疾病进展和癌症转移的关键，并将极大地有利于临床决策。近年来，成像技术的进步和适合临床应用的新型示踪剂的开发，使淋巴系统的成像在临床和临床前设置。在这篇综述中，我们重点介绍了近红外光谱(NIRS)、正电子发射断层扫描(PET)、计算机断层扫描(CT)、磁共振成像(MRI)和荧光光学成像等不同现代技术的优缺点，这些技术对该领域的研究产生了重大影响，并对病理状态的进展有了深入的了解。本综述还强调了使用当前的成像技术和免疫细胞标记特异性示踪剂来识别和跟踪淋巴系统中的免疫细胞，这将有助于了解免疫治疗方案中的疾病进展和缓解。

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引用次数: 3

Hydrodynamic model for renal microvascular filtration: Effects of physiological and hemodynamic changes on glomerular size-selectivity 肾微血管滤过的流体动力学模型:生理和血流动力学变化对肾小球大小选择性的影响

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2022-07-25 DOI: 10.1111/micc.12779

Numpong Punyaratabandhu, Panadda Dechadilok, Wannapong Triampo, Pisut Katavetin

Objective

The first step in renal urine formation is ultrafiltration across the glomerular barrier. The change in its nanostructure has been associated with nephrotic syndromes. Effects of physiological and hemodynamic factor alterations associated with diabetic nephropathy (DN) on glomerular permselectivity are examined through a mathematical model employing low-Reynolds-number hydrodynamics and hindered transport theory.

Methods

Glomerular capillaries are represented as networks of cylindrical tubes with multilayered walls. Glomerular basement membrane (GBM) is a fibrous medium with bimodal fiber sizes. Epithelial slit fiber spacing follows a lognormal distribution based on reported electron micrographs with the highest resolution. Endothelial fenestrae are filled with fibers the size of glycosaminoglycans (GAGs). Effects of fiber-macromolecule steric and hydrodynamic interactions are included. Focusing on diabetic nephropathy, the physiological and hemodynamic factors employed in the computation are those reported for healthy humans and patients with early-but-overt diabetic nephropathy. The macromolecule concentration is obtained as a finite element solution of the convection-diffusion equation.

Results

Computed sieving coefficients averaged along the capillary length agree well with ficoll sieving coefficients from studies in humans for most solute radii. GBM thickening and the loss of the slit diaphragm hardly affect glomerular permselectivity. GAG volume fraction reduction in the endothelial fenestrae, however, significantly increases macromolecule filtration. Increased renal plasma flow rate (RPF), glomerular hypertension, and reduction of lumen osmotic pressure cause a slight sieving coefficient decrease. These effects are amplified by an increased macromolecule size.

Conclusion

Our results indicate that glomerular hypertension and the reduction in the oncotic pressure decreases glomerular macromolecule filtration. Reduction of RPF and changes in the glomerular barrier structure associated with DN, however, increase the solute sieving. Damage to GAGs caused by hyperglycemia is likely to be the most prominent factor affecting glomerular size-selectivity.

目的肾尿形成的第一步是超滤过肾小球屏障。其纳米结构的变化与肾病综合征有关。通过采用低雷诺数流体动力学和阻碍转运理论的数学模型，研究了与糖尿病肾病(DN)相关的生理和血流动力学因子改变对肾小球过电选择性的影响。方法将肾小球毛细血管表示为具有多层壁的圆柱形管网络。肾小球基底膜(GBM)是一种纤维介质，具有双峰纤维大小。上皮狭缝纤维间距遵循对数正态分布，基于报道的电子显微图具有最高的分辨率。内皮窗内充满糖胺聚糖(GAGs)大小的纤维。包括纤维-大分子的空间和水动力相互作用的影响。针对糖尿病肾病，在计算中采用的生理和血流动力学因素是已报道的健康人和早期但明显的糖尿病肾病患者的生理和血流动力学因素。大分子浓度以对流扩散方程的有限元解的形式得到。结果沿毛细管长度计算的平均筛分系数与在大多数溶质半径的人类研究中得到的筛分系数吻合得很好。GBM增厚和狭缝膈的丧失几乎不影响肾小球的透性选择性。然而，内皮腔内GAG体积分数的降低显著增加了大分子滤过。肾血浆流速(RPF)升高、肾小球高血压和管腔渗透压降低导致筛分系数轻微降低。这些效应随着大分子大小的增加而被放大。结论肾小球高血压和肿瘤压降低可降低肾小球大分子滤过。然而，与DN相关的RPF减少和肾小球屏障结构的改变增加了溶质筛分。高血糖引起的gag损伤可能是影响肾小球大小选择性的最重要因素。

{"title":"Hydrodynamic model for renal microvascular filtration: Effects of physiological and hemodynamic changes on glomerular size-selectivity","authors":"Numpong Punyaratabandhu, Panadda Dechadilok, Wannapong Triampo, Pisut Katavetin","doi":"10.1111/micc.12779","DOIUrl":"10.1111/micc.12779","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The first step in renal urine formation is ultrafiltration across the glomerular barrier. The change in its nanostructure has been associated with nephrotic syndromes. Effects of physiological and hemodynamic factor alterations associated with diabetic nephropathy (DN) on glomerular permselectivity are examined through a mathematical model employing low-Reynolds-number hydrodynamics and hindered transport theory.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Glomerular capillaries are represented as networks of cylindrical tubes with multilayered walls. Glomerular basement membrane (GBM) is a fibrous medium with bimodal fiber sizes. Epithelial slit fiber spacing follows a lognormal distribution based on reported electron micrographs with the highest resolution. Endothelial fenestrae are filled with fibers the size of glycosaminoglycans (GAGs). Effects of fiber-macromolecule steric and hydrodynamic interactions are included. Focusing on diabetic nephropathy, the physiological and hemodynamic factors employed in the computation are those reported for healthy humans and patients with early-but-overt diabetic nephropathy. The macromolecule concentration is obtained as a finite element solution of the convection-diffusion equation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Computed sieving coefficients averaged along the capillary length agree well with ficoll sieving coefficients from studies in humans for most solute radii. GBM thickening and the loss of the slit diaphragm hardly affect glomerular permselectivity. GAG volume fraction reduction in the endothelial fenestrae, however, significantly increases macromolecule filtration. Increased renal plasma flow rate (RPF), glomerular hypertension, and reduction of lumen osmotic pressure cause a slight sieving coefficient decrease. These effects are amplified by an increased macromolecule size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results indicate that glomerular hypertension and the reduction in the oncotic pressure decreases glomerular macromolecule filtration. Reduction of RPF and changes in the glomerular barrier structure associated with DN, however, increase the solute sieving. Damage to GAGs caused by hyperglycemia is likely to be the most prominent factor affecting glomerular size-selectivity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10446988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1