Blood vessels

血管
  • 文章类型: Journal Article
    酪氨酸激酶(TKs)是由自磷酸化激活的催化酶,其通过磷酸化下游底物上的酪氨酸残基起作用。酪氨酸激酶抑制剂(TKIs)已被广泛用作癌症治疗,主要是由于它们在自噬中的作用,血管重塑和炎症。这表明酪氨酸激酶抑制是一种吸引人的治疗靶标,用于利用几种神经退行性疾病(NDD)病理的趋同机制。神经变性和癌症之间的重叠作用机制表明,TKIs可能在减轻神经变性过程中起关键作用。包括错误折叠或有毒蛋白质的降解,减少炎症和预防脑血管纤维化事件。在这次审查中,我们将讨论选择TK在各种疾病相关过程中的不同作用,以及确定已被探索作为治疗干预目标的TKs,以及正在研究作为NDD治疗方法的相关药物。
    Tyrosine kinases (TKs) are catalytic enzymes activated by auto-phosphorylation that function by phosphorylating tyrosine residues on downstream substrates. Tyrosine kinase inhibitors (TKIs) have been heavily exploited as cancer therapeutics, primarily due to their role in autophagy, blood vessel remodeling and inflammation. This suggests tyrosine kinase inhibition as an appealing therapeutic target for exploiting convergent mechanisms across several neurodegenerative disease (NDD) pathologies. The overlapping mechanisms of action between neurodegeneration and cancer suggest that TKIs may play a pivotal role in attenuating neurodegenerative processes, including degradation of misfolded or toxic proteins, reduction of inflammation and prevention of fibrotic events of blood vessels in the brain. In this review, we will discuss the distinct roles that select TKs have been shown to play in various disease-associated processes, as well as identify TKs that have been explored as targets for therapeutic intervention and associated pharmacological agents being investigated as treatments for NDDs.
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  • 文章类型: Journal Article
    作为循环系统的关键部分,血管将氧气和营养输送到身体的每个角落,滋养每个细胞,并清除废物和毒素。血管发育和功能缺陷与许多疾病密切相关。比如心脏病,中风,和动脉粥样硬化。在神经系统中,神经和血管系统在发育和功能上错综复杂。首先,外周血管和神经呈平行分布。在中枢神经系统(CNS),神经和血管形成一个复杂的界面,称为神经血管单元。第二,血管系统利用与神经系统相似的细胞和分子机制进行发育。第三,中枢神经系统血管的发育和功能受到中枢神经系统特异性信号通路和神经活动的严格调控。此外,中枢神经系统内的血管内皮细胞与周细胞紧密相连并相互作用,星形胶质细胞,神经元,和小胶质细胞形成血脑屏障(BBB)。血脑屏障严格控制血液和大脑之间的物质交换,维持大脑的微环境稳态,这对中枢神经系统的正常发育和功能至关重要。这里,对血管和血脑屏障发育的神经调控研究进行了全面总结,并提出了未来的研究方向。
    As a critical part of the circulatory system, blood vessels transport oxygen and nutrients to every corner of the body, nourishing each cell, and also remove waste and toxins. Defects in vascular development and function are closely associated with many diseases, such as heart disease, stroke, and atherosclerosis. In the nervous system, the nervous and vascular systems are intricately connected in both development and function. First, peripheral blood vessels and nerves exhibit parallel distribution patterns. In the central nervous system (CNS), nerves and blood vessels form a complex interface known as the neurovascular unit. Second, the vascular system employs similar cellular and molecular mechanisms as the nervous system for its development. Third, the development and function of CNS vasculature are tightly regulated by CNS-specific signaling pathways and neural activity. Additionally, vascular endothelial cells within the CNS are tightly connected and interact with pericytes, astrocytes, neurons, and microglia to form the blood-brain barrier (BBB). The BBB strictly controls material exchanges between the blood and brain, maintaining the brain\'s microenvironmental homeostasis, which is crucial for the normal development and function of the CNS. Here, we comprehensively summarize research on neural regulation of vascular and BBB development and propose directions for future research.
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  • 文章类型: Journal Article
    髂内动脉作为髂总动脉的末端延伸而出现,并向骨盆区域供应血液。这项研究旨在确定墨西哥人群样本中髂内动脉(IIA)的解剖变异。这是一项回顾性的横断面观察研究。包括通过股动脉入路对接受各种医疗程序的患者进行的81例血管造影。通过评估血管造影图像来识别IIA分支模式的变化,并根据Adachi的分类将其分为五种类型(I-V)。总共分析了139个半骨盆(右78个,左61个)。每种类型的变化频率如下:I型(71.2%),II型(10.79%),III型(0例),第四类(0.7%),V型(12.94%),和未分类(4.31%)。墨西哥西部人口样本中IIA最常见的解剖变异是I型,其次是V型和II型。尽管V型在大多数人群中很少见,它是本研究中第二常见的变异。了解IIA分支模式的变体对于在骨盆区域进行精确的侵入性手术并最大程度地减少并发症是必要的。
    The internal iliac artery arises as a terminal extension of the common iliac artery and supplies blood to the pelvic region. This study aims to identify the anatomic variations of the internal iliac artery (IIA) in a Mexican population sample. This is a retrospective cross-sectional observational study. A total of 81 angiographies via the femoral artery approach performed on patients undergoing various medical procedures were included. Variations in the IIA branching patterns were identified by evaluating the angiographic images and grouped according to Adachi\'s classification into five types (I-V). A total of 139 hemipelvises were analyzed (78 right and 61 left). The frequencies of each type of variation were as follows: Type I (71.2%), Type II (10.79%), Type III (0 cases), Type IV (0.7%), Type V (12.94%), and unclassified (4.31%). The most frequent anatomical variants of the IIA in the western Mexican population sample were Type I, followed by Types V and II. Even though Type V is rare in most populations, it was the second most frequent variant in this study. Understanding the variants of the IIA branching pattern is necessary for performing invasive procedures in the pelvic region with precision and minimizing complications.
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  • 文章类型: Journal Article
    在胎儿发育中,组织相互作用,例如血管(BV)和上皮组织之间的相互作用对于器官发生至关重要。在这里,我们概述了肝上皮组织和门静脉之间的空间排列,以观察人诱导多能干细胞(hiPSC)的肝内胆管(BD)的形成。我们在由未成熟平滑肌细胞和内皮细胞组成的人工BV上共培养hiPSC-肝祖细胞,两者都来自hiPSC。3周后,hiPSC-BV整合的肝类器官(BVLO)内的肝祖细胞分化为胆管细胞并获得上皮特征,包括细胞间连接,根尖膜上的微绒毛,和分泌功能。此外,肝表面移植-BVLO可暂时减轻胆汁淤积性损伤症状。单细胞RNA序列分析表明BD通过TGFβ和Notch途径与BVLO中的BV相互作用。敲除hiPSC-BV中的JAG1显著减弱胆管形成,强调BVLO作为Alagille综合征模型的潜力,先天性胆道疾病.总的来说,我们开发了一种新型的3D共培养方法,该方法通过模拟肝脏上皮-BV相互作用成功建立了功能性人类BD。
    In fetal development, tissue interaction such as the interplay between blood vessel (BV) and epithelial tissue is crucial for organogenesis. Here we recapitulate the spatial arrangement between liver epithelial tissue and the portal vein to observe the formation of intrahepatic bile ducts (BDs) from human induced pluripotent stem cells (hiPSC). We co-culture hiPSC-liver progenitors on the artificial BV consisting of immature smooth muscle cells and endothelial cells, both derived from hiPSCs. After 3 weeks, liver progenitors within hiPSC-BV-incorporated liver organoids (BVLO) differentiate to cholangiocytes and acquire epithelial characteristics, including intercellular junctions, microvilli on the apical membrane, and secretory functions. Furthermore, liver surface transplanted-BVLO temporarily attenuates cholestatic injury symptoms. Single cell RNA sequence analysis suggests that BD interact with the BV in BVLO through TGFβ and Notch pathways. Knocking out JAG1 in hiPSC-BV significantly attenuates bile duct formation, highlighting BVLO potential as a model for Alagille syndrome, a congenital biliary disease. Overall, we develop a novel 3D co-culture method that successfully establishes functional human BDs by emulating liver epithelial-BV interaction.
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  • 文章类型: Journal Article
    去分化脂肪肉瘤(DDLPS)是非脂肪源性肉瘤,通常来自高分化脂肪肉瘤(WDLPS),虽然它可以从头发展。DDLPS肿瘤很少转分化为非脂肪间充质组织;然而,后者缺乏明显的多样性,主要表现为横纹肌或成骨/软骨分化。这里,我们报告一例DDLPS,其中包含大量非典型血管.一个60多岁的男人在他的右大腿上出现了一个大肿瘤,手术切除了肿瘤.微观上,大多数肿瘤是WDLPS,但是一小部分显示了DDLPS,由高级梭形细胞组成。值得注意的是,DDLPS包含具有非典型细胞结构的各种大小的血管,包括看似肌肉层的血管。免疫组织化学,血管壁内的非典型细胞表达aSMA,与平滑肌细胞或周细胞一致,而周围的高级梭形细胞只局部表达,血管内的这些aSMA阳性细胞通过免疫荧光原位杂交表现出MDM2扩增。我们的结果表明,DDLPS可以转分化为各种大小的伴随血管的平滑肌细胞,这可能支持他们的生存和扩散。
    Dedifferentiated liposarcoma (DDLPS) is a non-lipogenic sarcoma, generally arising from well-differentiated liposarcoma (WDLPS), although it can develop de novo. DDLPS tumors rarely trans-differentiate into non-adipose mesenchymal tissues; however, the latter lack notable variety and mostly show striated muscle or osteogenic/chondrogenic differentiation. Here, we report a case of DDLPS that contained numerous atypical vessels. A man in his sixties presented with a large tumor in his right thigh, and the tumor was surgically resected. Microscopically, most of the tumor was WDLPS, but a minor portion showed DDLPS, consisting of high-grade spindle cells. Remarkably, the DDLPS contained vessels of various sizes with atypical cytoarchitecture, including vessels with seemingly muscular layers. Immunohistochemically, the atypical cells within the vascular wall expressed aSMA, consistent with smooth muscle cells or pericytes, whereas surrounding high-grade spindle cells only focally expressed it, and these aSMA-positive cells within the vessels exhibited MDM2 amplification by immuno-fluorescence in situ hybridization. Our results demonstrate that DDLPS can trans-differentiate into smooth muscle cells of various-sized accompanying vessels, which may support their survival and proliferation.
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  • 文章类型: Case Reports
    血管平滑肌瘤,血管平滑肌的良性肿瘤,主要影响30-50岁的人,女性发病率较高。虽然它通常会影响下肢,它也可以在头部和颈部发展。然而,下咽血管平滑肌瘤极为罕见,世界文学中只有一个记录在案的案例。
    作者介绍了一个罕见的病例,一个70岁的男性,有声音改变和吞咽不适的症状。影像学检查提示下咽肿块。直接喉镜检查显示一个明确的肿块,起源于左咽侧壁,阻塞左牙和梨状窦。患者接受了前外侧咽切开术和肿块切除术。
    咽前外侧手术成功后,患者的症状明显改善。
    下咽血管平滑肌瘤由于其不寻常的位置而具有挑战性。它的稀有性强调了在评估下咽肿块时将其视为可能的差异的重要性。
    UNASSIGNED: Angioleiomyoma, a benign tumour of the smooth muscles of blood vessels, primarily affects individuals aged 30-50 years, with a higher incidence in females. While it commonly affects the lower extremities, it can also develop in the head and neck. However, hypopharyngeal angioleiomyomas are extremely rare, with only one documented case in world literature.
    UNASSIGNED: The authors present a rare case of a 70-year-old male with symptoms of voice change and deglutition discomfort. Imaging studies indicated a hypopharyngeal mass. Direct laryngoscopy showed a well-defined mass originating from the left lateral pharyngeal wall, obstructing the left vallecula and pyriform sinus. The patient underwent anterolateral pharyngotomy with mass excision.
    UNASSIGNED: After a successful anterolateral pharyngotomy, the patient experienced significant improvement in symptoms.
    UNASSIGNED: Diagnosing and managing hypopharyngeal angioleiomyoma is challenging due to its unusual location. Its rarity emphasizes the importance of considering it as a possible differential when evaluating hypopharyngeal masses.
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  • 文章类型: Journal Article
    植物提取物(PE)是从植物中提取的天然物质,富含各种生物活性成分。探索PE血管保护作用的分子机制和相互作用有助于进一步制定保护衰老血管的策略。对于这篇评论,内容来自PubMed等科学数据库,中国国家知识基础设施(CNKI),和截至2024年7月的谷歌学者,使用搜索词“植物提取物”,“氧化应激”,“血管老化”,“内皮功能障碍”,\"ROS\",和“炎症”。本文综述了PE对衰老血管的保护作用。通过清除活性氧等途径,激活抗氧化剂信号通路,增强呼吸链复合物的活性,抑制线粒体活性氧的产生,提高一氧化氮的生物利用度,下调炎症因子的分泌,并激活沉默调节蛋白1和Nrf2信号通路,它可以改善由年龄相关的氧化应激引起的血管结构和功能变化,线粒体功能障碍,和老化引起的炎症,从而降低与年龄有关的心血管疾病的发病率。
    Plant Extracts (PE) are natural substances extracted from plants, rich in various bioactive components. Exploring the molecular mechanisms and interactions involved in the vascular protective effects of PE is beneficial for the development of further strategies to protect aging blood vessels. For this review, the content was obtained from scientific databases such as PubMed, China National Knowledge Infrastructure (CNKI), and Google Scholar up to July 2024, using the search terms \"Plant extracts\", \"oxidative stress\", \"vascular aging\", \"endothelial dysfunction\", \"ROS\", and \"inflammation\". This review highlighted the effects of PE in protecting aging blood vessels. Through pathways such as scavenging reactive oxygen species, activating antioxidant signaling pathways, enhancing respiratory chain complex activity, inhibiting mitochondrial-reactive oxygen species generation, improving nitric oxide bioavailability, downregulating the secretion of inflammatory factors, and activating sirtuins 1 and Nrf2 signaling pathways, it can improve vascular structural and functional changes caused by age-related oxidative stress, mitochondrial dysfunction, and inflammation due to aging, thereby reducing the incidence of age-related cardiovascular diseases.
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    文章类型: English Abstract
    目的:调查年龄的影响,各种荷尔蒙水平,勃起功能障碍(ED)患者阴茎海绵体血管功能的生化指标。方法:回顾性分析2020年1月至2023年8月在北京大学第三医院生殖医学中心行彩色多普勒超声(CDDU)和海绵体内注射试验(ICI)的男性ED患者的临床资料。使用SPSS29.0对数据进行管理和处理,并进行多变量Logistic回归分析。
    结果:共纳入700例ED患者,380例ICI结果为阴性,320例呈阳性。在研究中,84例患者收缩期峰值流速(PSV)<25cm/s,616例PSV≥25cm/s;202例患者舒张末期流速(EDV)>5cm/s,498例EDV≤5cm/s。264例患者有异常的PSV和/或EDV结果,436对两者都有正常结果。血管性ED患者的雌激素水平明显降低(t=-3.546,P<0.001)。睾酮水平降低(t=-2.089,P=0.037),与非血管性ED相比,高血糖发生率更高(χ2=12.772,P=0.002)。动脉性ED患者年龄较大(t=3.953,P<0.001),高血糖发生率较高(χ2=9.518,P=0.009),与非动脉ED患者相比,雌激素/睾酮比率更高(t=2.330,P=0.020)。混合动静脉ED患者年龄较高(t=3.567,P<0.001),睾酮水平降低(t=-2.288,P=0.022),高血糖发生率较高(χ2=12.877,P=0.002),与正常结果相比,雌激素/睾酮比率更大(t=2.096,P=0.037)。多因素Logistic回归分析显示,雌激素水平升高是血管ED的保护因素(OR=1.009,95CI:1.004-1.014),血糖≥7.0mmol/L是危险因素(OR=0.381,95CI:0.219~0.661)。高龄是动脉性ED的危险因素(OR=0.960,95CI:0.938-0.982)。此外,年龄较大(OR=0.976,95CI:0.958-0.993)和葡萄糖水平为5.6-6.9mmol/L(OR=0.591,95CI:0.399-0.876)也是混合动静脉ED的危险因素.
    结论:高血糖和衰老可能损害阴茎海绵体血管功能,而较高水平的雌激素可能对其有保护作用。
    OBJECTIVE: To investigate the impact of age, various hormonal levels, and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction (ED). Me-thods: A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography (CDDU) and intracavernosal injection test (ICI) at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023. Data were managed and processed using SPSS 29.0, and a multivariable Logistic regression analysis was conducted.
    RESULTS: A total of 700 ED patients were included, with 380 showing negative ICI results and 320 positive. In the study, 84 patients had a peak systolic velocity (PSV) < 25 cm/s, while 616 had PSV≥25 cm/s; 202 patients had end-diastolic velocity (EDV)>5 cm/s, and 498 had EDV≤5 cm/s. 264 patients had abnormal PSV and/or EDV results, and 436 had normal results for both. Patients with vascular ED had significantly lower estrogen levels (t=-3.546, P < 0.001), lower testosterone levels (t=-2.089, P=0.037), and a higher rate of hyperglycemia (χ2=12.772, P=0.002) compared with those with non-vascular ED. The patients with arterial ED were older (t=3.953, P < 0.001), had a higher rate of hyperglycemia (χ2=9.518, P=0.009), and a higher estrogen/testosterone ratio (t=2.330, P=0.020) compared with those with non-arterial ED. The patients with mixed arteriovenous ED had higher age (t=3.567, P < 0.001), lower testosterone levels (t=-2.288, P=0.022), a higher rate of hyperglycemia (χ2=12.877, P=0.002), and a larger estrogen/testosterone ratio (t=2.096, P=0.037) compared with those with normal findings. Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED (OR=1.009, 95%CI: 1.004-1.014), and glucose≥7.0 mmol/L was a risk factor (OR=0.381, 95%CI: 0.219-0.661). Older age was a risk factor for arterial ED (OR=0.960, 95%CI: 0.938-0.982). Additionally, older age (OR=0.976, 95%CI: 0.958-0.993) and glucose levels of 5.6-6.9 mmol/L (OR=0.591, 95%CI: 0.399-0.876) were also risk factors for mixed arterio-venous ED.
    CONCLUSIONS: Hyperglycemia and aging may impair penile cavernous body vascular function, while higher levels of estrogen may have a protective effect on it.
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  • 文章类型: Journal Article
    背景:作为基因表达的关键调节因子,microRNAs影响许多心血管机制,并与几种心血管疾病有关。在这项研究中,我们的目的是研究全血microRNAs与血管功能的几个定量测量的关系,并通过整合microRNA-基因表达分析探讨其生物学作用。
    方法:通过RNA-Seq对2606名参与者(45.8%男性,平均年龄:53.93岁,年龄范围:30至95岁)来自莱茵兰研究,波恩正在进行的基于人群的队列研究,德国。使用加权基因共表达网络分析将具有高度相关表达水平的microRNA聚类为14个模块。通过线性回归模型,我们调查了每个模块的表达与血管健康的定量标志物之间的关联,包括脉搏波速度,总动脉顺应性指数,心脏指数,中风指数,全身血管阻力指数,反应性皮肤充血和白质高强度负荷。对于与至少一个特征关联的每个模块,定义了一个或多个驱动关联的hub-microRNA.通过定位到推定的靶基因,随后进行基因本体论途径分析,进一步表征了Hub-microRNA。
    结果:四个模块,由hub-microRNAsmiR-320家族代表,miR-378家族,miR-3605-3p,miR-6747-3p,miR-6786-3p,还有miR-330-5p,与总动脉顺应性指数相关。重要的是,miR-320家族模块也与白质高强度负荷相关,部分通过动脉顺应性介导的作用。此外,hub-microRNAmiR-192-5p与心脏指数相关。功能分析证实了所鉴定的microRNAs与血管功能的相关性,其中,富集参与血管形态发生和发育的途径,血管生成,端粒的组织和维护,和胰岛素分泌。
    结论:我们鉴定了几种与心血管功能密切相关的微小RNA,尤其是动脉顺应性和心输出量.此外,我们的结果强调miR-320是脑血管损伤的调节因子,部分通过调节血管功能。由于许多这些microRNAs参与与血管发育和衰老相关的生物过程,我们的研究结果有助于对血管生理学的理解,并为心血管疾病的预防提供了可能的目标.
    BACKGROUND: As key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis.
    METHODS: Peripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module\'s expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis.
    RESULTS: Four modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion.
    CONCLUSIONS: We identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.
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  • 文章类型: Journal Article
    生物工程和再生医学策略有望用于血管疾病的治疗。然而,当前的局限性抑制了这些方法转化为临床实践的能力。在这里,我们总结了在主动脉瘤的疾病应用中抑制血管再生的一些主要瓶颈,中风,和外周动脉疾病。我们还描述了阻止组织工程应用的血管网络三维生物打印的瓶颈。最后,我们描述了克服这些挑战以促进血管再生的新兴技术和机遇。
    Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration.
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