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Investigation the effects of 2-aminoethoxydiphenyl borate (2-APB) on aminoglycoside nephrotoxicity. 2-氨基乙氧基二苯硼酸酯(2-APB)对氨基糖苷肾毒性的影响。
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-01-02 Epub Date: 2024-01-09 DOI: 10.1080/01913123.2023.2278629
Özge Kendirlinan, Yurdun Kuyucu, Bilge Güzelel, Ebru Dündar Yenilmez, Abdullah Tuli, Gülşah Seydaoğlu, Ufuk Özgü Mete

Investigation the protective effect of transient receptor potential channel modulator 2-Aminoethoxydiphenyl Borate (2-APB) on aminoglycoside nephrotoxicity caused by reactive oxygen species, calcium-induced apoptosis and inflammation was aimed. Forty Wistar rats were divided (n=8) as follows: Control group; DMSO group; 2-APB group; Gentamicin group (injected 100 mg/kg gentamicin intramuscularly for 10 days); Gentamicin+ 2-APB group (injected 2 mg/kg 2-APB intraperitoneally, then after 30 minutes 100 mg/kg gentamicin was injected intramuscularly for 10 days). Blood samples were collected for biochemical analyses, kidney tissue samples were collected for light, electron microscopic and immunohistochemical investigations. In gentamicin group glomerular degeneration, tubular dilatation, vacuolization, desquamation of tubular cells and hyaline cast formation in luminal space and leukocyte infiltration were seen. Disorganization of microvilli of tubular cells, apical cytoplasmic blebbing, lipid accumulation, myelin figure like structure formation, increased lysosomes, mitochondrial swelling and disorganization of cristae structures, apoptotic changes and widening of intercellular space were found. TNF-α, IL-6 and caspase 3 expressions were increased. BUN and creatinine concentrations were increased. Increase in MDA levels and decrease in SOD activities were determined. Even though degeneration still continues in gentamicin+2-APB treatment group, severity and the area it occupied were decreased and the glomerular and tubule structures were generally preserved. TNF-α, IL-6, caspase 3 immunoreactivities and BUN, creatinine, MDA concentrations were reduced and SOD activities were increased markedly compared to gentamicin group. In conclusion, it has been considered that 2-APB can prevent gentamicin mediated nephrotoxicity with its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

研究瞬时受体电位通道调节剂2-氨基乙氧基二苯硼酸盐(2-APB)对活性氧、钙诱导的细胞凋亡和炎症引起的氨基糖苷肾毒性的保护作用。Wistar大鼠40只(n=8),随机分为:对照组;DMSO组;2-APB组;庆大霉素组(肌肉注射庆大霉素100 mg/kg,持续10 d);庆大霉素+ 2- apb组(腹腔注射2 mg/kg 2- apb, 30 min后肌肉注射100 mg/kg庆大霉素,持续10 d)。采集血液样本进行生化分析,采集肾脏组织样本进行光镜、电镜和免疫组化检查。庆大霉素组可见肾小球变性、小管扩张、空泡化、小管细胞脱屑、管腔内透明样样形成及白细胞浸润。小管细胞微绒毛紊乱,顶端胞浆泡状,脂质堆积,髓鞘图状结构形成,溶酶体增多,线粒体肿胀,嵴结构紊乱,细胞凋亡改变,细胞间隙增宽。TNF-α、IL-6、caspase 3表达升高。BUN和肌酐浓度升高。MDA水平升高,SOD活性降低。庆大霉素+2-APB治疗组尽管变性仍在继续,但其严重程度和占地面积均有所降低,肾小球和小管结构基本保留。与庆大霉素组相比,TNF-α、IL-6、caspase 3免疫反应活性和BUN、肌酐、MDA浓度显著降低,SOD活性显著升高。综上所述,2-APB具有抗氧化、抗凋亡和抗炎作用,可预防庆大霉素介导的肾毒性。
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引用次数: 0
Intracellular organelles remodeling in myocardial endotheliocytes in COVID-19: an autopsy-based study. COVID-19患者心肌内皮细胞胞内细胞器重构:一项基于尸检的研究
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2024-01-02 Epub Date: 2024-01-09 DOI: 10.1080/01913123.2023.2286977
Nataliya Bgatova, Sergey Savchenko, Alexei Lamanov, Iuliia Taskaeva, Boris Ayzikovich, Valentina Gritcinger, Andrey Letyagin, Maksim Korolev

It is known that the unfavorable outcome in patients infected with SARS-CoV-2 may be associated with the development of complications caused by heart damage due to the direct virus action. The mechanism of these cardiovascular injuries caused by SARS-CoV-2 infection has not been fully understood; however, the study of COVID-19-associated myocardial microcirculatory dysfunction can represent the useful strategy to solving this challenge. Thus, here we aimed to study the ultrastructural organization of endothelial cells of myocardial capillaries in patients with COVID-19. The morphology of endotheliocytes of the myocardial blood capillaries in patients with COVID-19 was studied on cardiac autopsy material using transmission electron microscopy. The endotheliocytes of myocardial capillaries in patients with COVID-19 were characterized by the abundant rough endoplasmic reticulum (ER) membranes, the Golgi complex, and free polysomal complexes of ribosomes and lipids. The presence of double membrane vesicles with virions and zippered ER was detected in the cytoplasm of endotheliocytes. The revealed endothelial ultrastructural changes indicate the remodeling of intracellular membranes during SARS-CoV-2 infection. Our findings confirm the formation of virus-induced structures in myocardial endothelial cells considered critical for viral replication and assembly. The data may elucidate the mechanisms of endothelial dysfunction development in patients with COVID-19 to provide potential targets for drug therapy.

已知,感染SARS-CoV-2的患者的不良结果可能与病毒直接作用引起的心脏损伤并发症的发生有关。这些由SARS-CoV-2感染引起的心血管损伤机制尚不完全清楚;然而,对covid -19相关心肌微循环功能障碍的研究可以代表解决这一挑战的有用策略。因此,我们旨在研究COVID-19患者心肌毛细血管内皮细胞的超微结构组织。用透射电镜观察新冠肺炎患者心肌毛细血管内皮细胞形态。新冠肺炎患者心肌毛细血管内皮细胞具有丰富的粗内质网(ER)膜、高尔基复合物、游离核糖体和脂质多体复合物等特征。内皮细胞细胞质中存在双膜囊泡,内含病毒粒子和拉链内质网。内皮细胞超微结构的改变提示了SARS-CoV-2感染期间细胞膜的重塑。我们的发现证实了心肌内皮细胞中病毒诱导结构的形成被认为是病毒复制和组装的关键。这些数据可能阐明COVID-19患者内皮功能障碍发展的机制,为药物治疗提供潜在靶点。
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引用次数: 0
Myxoinflammatory fibroblastic sarcoma: ultrastructural study of 7 cases 肌炎性纤维肉瘤:7 个病例的超微结构研究
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-12-21 DOI: 10.1080/01913123.2023.2292559
Guillermo Ernesto Corredor-Alonso, Claudia Haydee Sarai Caro-Sánchez, Hugo Ricardo Domínguez-Malagón
Since first described, several studies about Myxoinflammatory fibroblastic sarcomas (MIFS) have been published stating the clinicopathological, morphological and immunohistochemical features. Howev...
自首次被描述以来,已有多项关于肌炎性成纤维肉瘤(MIFS)的研究发表,阐述了其临床病理学、形态学和免疫组化特征。然而...
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引用次数: 0
Punctate IgG staining particles localize in the budding ballooning clusters of reactive foot processes in minimal change disease 点状 IgG 染色颗粒定位在极小病变中反应性足部过程的萌芽气球团中
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-12-14 DOI: 10.1080/01913123.2023.2292590
Ping L. Zhang, Vasudevan D. Mahalingam, Brandon D. Metcalf, Yazan A. Al-Othman, Wei Li, Hassan D. Kanaan, Guillermo A. Herrera
The etiology of minimal change disease (MCD) remains a mystery as the only characteristic findings are the diffuse effacement of foot processes seen on electron microscopy (EM). Punctate IgG staini...
微小病变病(MCD)的病因至今仍是一个谜,因为其唯一的特征性结果就是电子显微镜(EM)上看到的足突弥漫性渗出。点状IgG染色是一种常见的病理诊断方法。
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引用次数: 0
Comparative effects of chemical and green zinc oxide nanoparticles in caprine testis: ultrastructural and steroidogenic enzyme analysis 化学纳米颗粒和绿色纳米氧化锌对黄羊睾丸影响的比较:超微结构和类固醇生成酶分析
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-12-12 DOI: 10.1080/01913123.2023.2286963
Sneha Bareja, Rajnesh Kumar Sharma
Recent advancements in nanotechnology has opened up enormous possibilities in diverse sectors such as industries, agriculture, environmental remediation, electronics, medicine and varied industries...
纳米技术的最新进展为工业、农业、环境修复、电子学、医学和各行各业等不同领域带来了巨大的可能性......
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引用次数: 0
The Protective effects of Vitamin E against alterations of rat testis structure induced by deltamethrin; histological, ultrastructure, and biochemical study 维生素 E 对溴氰菊酯引起的大鼠睾丸结构改变的保护作用;组织学、超微结构和生化研究
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-12-10 DOI: 10.1080/01913123.2023.2292563
Ghada Nady Ouais, Sherif A. Kamar, Ali Ahmed Mousa, Mohamed Mostafa Sonbol
Deltamethrin is a widely used synthetic pyrethroid pesticide. It causes reproductive toxicity. Aim of the work: it evaluates the impact of vitamin E in restoration of the testicular integrity of al...
溴氰菊酯是一种广泛使用的合成拟除虫菊酯杀虫剂。它会导致生殖毒性。工作目的:评估维生素 E 对恢复睾丸完整性的影响。
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引用次数: 0
The possible protective role of selenium on the visual cortex of adult albino rat on exposure to potassium dichromate. 硒对重铬酸钾暴露于成年白化病大鼠视觉皮层的可能保护作用。
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-11-02 Epub Date: 2023-11-30 DOI: 10.1080/01913123.2023.2259455
Sally S Anwer, Hala Mohamed Hassanin

The visual cortex is very important in mammals for processing of visual information. Exposure to heavy metals such as potassium dichromate poses serious health threat to human beings. The aim of this work is to study the effect of potassium dichromate on the visual cortex of adult albino rat and also to identify the possibility of selenium as protective agent against toxicity of potassium dichromate. A total number of 40 adult albino rats weighting (200-250) gm were used. They divided into four groups: control group, potassium dichromate received group, potassium dichromate and selenium received group and selenium received group. The rats received treatment for 6 weeks. After 6 weeks, they were sacrificed. The present study showed that potassium dichromate causes degeneration of granular neurons in layer IV and pyramidal neurons in layer V. Morphometric results revealed statistically significant decrease in the number of granule and pyramidal cells in potassium dichromate received group as compared with control group. Most of degenerative changes are improved by selenium.

视觉皮层在哺乳动物处理视觉信息方面非常重要。接触重铬酸钾等重金属对人类健康构成严重威胁。本工作的目的是研究重铬酸钾对成年白化大鼠视觉皮层的影响,并确定硒作为重铬酸钾毒性保护剂的可能性。总共使用了40只体重(200-250)克的成年白化大鼠。他们分为四组:对照组、重铬酸钾治疗组、重铬酸钾加硒治疗组和硒治疗组。大鼠接受6 周。6周后处死。本研究表明,重铬酸钾可导致IV层颗粒神经元和V层锥体神经元变性。形态计量学结果显示,与对照组相比,接受重铬酸钾治疗组的颗粒细胞和锥体细胞数量在统计学上显著减少。硒能改善大多数退行性变化。
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引用次数: 0
Adverse neurological effects after exposure to copper, manganese, and mercury mixtures in a Spraque-Dawley rat model: an ultrastructural investigation. Spraque-Dawley大鼠模型暴露于铜、锰和汞混合物后的神经系统不良反应:超微结构研究。
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-11-02 Epub Date: 2023-11-30 DOI: 10.1080/01913123.2023.2270580
Maxine Draper, Megan Jean Bester, Mia-Jeanne Van Rooy, Hester Magdalena Oberholzer

Exposure to environmental metal pollutants is linked to oxidative stress and the subsequent development of neurological disease. In this study, the effects of copper, manganese, and mercury, were evaluated at X100 the World Health Organization safety limits for drinking water. Using a Sprague-Dawley rat model, following exposure for 28 days, the effects of these metals on biochemical blood parameters and tissue and cellular structure of the brain were determined. Biochemical analysis revealed no hepatocellular injury with minor changes associated with the hepatobiliary system. Minimal changes were found for renal function and the Na+/K+ ratio was reduced in the copper and manganese (Cu + Mn) and copper, manganese, and mercury (Cu, Mn + Hg) groups that could affect neurological function. Light microscopy of the brain revealed abnormal histopathology of Purkinje cells in the cerebellum and pyramidal cells in the cerebrum as well as tissue damage and fibrosis of the surface blood vessels. Transmission electron microscopy of the cerebral neurons showed microscopic signs of axonal damage, chromatin condensation, the presence of indistinct nucleoli and mitochondrial damage. Together these cellular features suggest the presence and influence of oxidative stress. Exposure to these metals at X100 the safety limits, as part of mixtures, induces changes to neurological tissue that could adversely influence neurological functioning in the central nervous system.

暴露于环境金属污染物与氧化应激和随后的神经疾病发展有关。在这项研究中,铜、锰和汞的影响在世界卫生组织饮用水安全限值X100下进行了评估。使用Sprague-Dawley大鼠模型,暴露28 天,测定了这些金属对血液生化参数以及大脑组织和细胞结构的影响。生化分析显示没有肝细胞损伤和与肝胆系统相关的轻微变化。肾功能变化很小,铜和锰(Cu + Mn)和铜、锰和汞(Cu、Mn + Hg)组可能影响神经功能。大脑光学显微镜显示小脑浦肯野细胞和大脑锥体细胞的组织病理学异常,以及表面血管的组织损伤和纤维化。大脑神经元的透射电子显微镜显示轴突损伤、染色质浓缩、核仁模糊和线粒体损伤的微观迹象。这些细胞特征共同表明氧化应激的存在和影响。作为混合物的一部分,在X100安全极限下暴露于这些金属会导致神经组织发生变化,从而对中枢神经系统的神经功能产生不利影响。
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引用次数: 0
The Sonic hedgehog pathway inhibitor GDC0449 induces autophagic death in human Medulloblastoma Daoy cells. Sonic hedgehog通路抑制剂GDC0449诱导人髓母细胞瘤day细胞自噬死亡。
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-11-02 Epub Date: 2023-11-30 DOI: 10.1080/01913123.2023.2270676
Qi Zhang, Wanjing Zou, Longtao He, Cuiping Zhang, Ying Wang

Medulloblastoma (MB) is a frequently occurring malignant brain tumor in children, and many of these tumors are identified by the abnormal activation of the Sonic Hedgehog (SHH) pathway. Although the Shh inhibitor GDC0449 initially shows some effectiveness in certain tumors, they eventually recur due to drug resistance mechanisms, highlighting the need for new treatment options. In this study, we explore whether GDC0449 induces autophagy in the human MB cell lines. To investigate the ultrastructural pathology changes of GDC0449-treated Daoy and D283 cells, we employed Transmission Electron Microscopy (TEM) technology to identify the expression of autophagic vacuoles. Our results indicate that GDC0449 only increases autophagy in Daoy cells by increasing the LC3-II/LC3-I ratio and autophagosome formation.We also analyzed Beclin1, LC3, Bax, and Cleaved-caspase3 protein and mRNA expression levels of autophagic and apoptotic markers using fluorescence confocal microscopy, RT-PCR, and Western blot. We found that cell autophagy and apoptosis increased in a dose-dependent manner with GDC0449 treatment. Additionally, we observed increased mammalian target of rapamycin (mTOR) phosphorylation and decreased protein kinase B (AKT/PKB), Ribosomal Protein S6, eIF4E-binding protein (4EBP1) phosphorylation in GDC0449-treated Daoy cells. It was observed that inhibiting autophagy using Beclin1 siRNA significantly blocked the apoptosis-inducing effects of GDC0449, suggesting that GDC0449 mediates its apoptotic effects by inducing autophagy.Our data suggests that GDC0449 inhibits the growth of human MB Daoy cells by autophagy-mediated apoptosis. The mechanism of GDC0449-induced autophagy in Daoy cells may be related to the inhibition of the PI3K/AKT/mTOR signaling pathway.

髓母细胞瘤(Medulloblastoma, MB)是一种常见于儿童的恶性脑肿瘤,其中许多肿瘤是通过异常激活Sonic Hedgehog (SHH)通路来识别的。尽管Shh抑制剂GDC0449最初在某些肿瘤中显示出一定的有效性,但由于耐药机制,它们最终会复发,这突出了对新治疗方案的需求。在本研究中,我们探讨GDC0449是否诱导人MB细胞系自噬。为了研究gdc0449处理后的day和D283细胞的超微结构病理变化,我们采用透射电镜(TEM)技术检测了自噬空泡的表达。我们的研究结果表明,GDC0449仅通过增加LC3-II/LC3-I比例和自噬体形成来增加day细胞的自噬。我们还使用荧光共聚焦显微镜、RT-PCR和Western blot分析了Beclin1、LC3、Bax和Cleaved-caspase3蛋白和自噬和凋亡标志物的mRNA表达水平。我们发现GDC0449治疗后细胞自噬和凋亡呈剂量依赖性增加。此外,我们观察到在gdc0449处理的day细胞中,哺乳动物雷帕霉素(mTOR)磷酸化靶点增加,蛋白激酶B (AKT/PKB)、核糖体蛋白S6、eif4e结合蛋白(4EBP1)磷酸化降低。我们观察到,使用Beclin1 siRNA抑制自噬可显著阻断GDC0449诱导凋亡的作用,提示GDC0449通过诱导自噬介导其凋亡作用。我们的数据表明,GDC0449通过自噬介导的凋亡抑制人MB day细胞的生长。gdc0449诱导day细胞自噬的机制可能与抑制PI3K/AKT/mTOR信号通路有关。
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引用次数: 0
Involvement of small leucine-rich proteoglycans and telocytes in thin and thick human endometrium: immunohistochemical and ultrastructural examination. 富含亮氨酸的小蛋白多糖和端粒细胞在薄和厚人类子宫内膜中的参与:免疫组织化学和超微结构检查。
IF 1 4区 医学 Q4 MICROSCOPY Pub Date : 2023-11-02 Epub Date: 2023-11-30 DOI: 10.1080/01913123.2023.2270660
Ozlem Karabay Akgul, Tugba Ekiz-Yilmaz

Thin endometrium, defined as an endometrial thickness of less than 7 mm during the late follicular phase, is a common cause of frequent cancelation of embryo transfers or recurrent implantation failure during assisted reproductive treatment. Small proteoglycans regulate intracellular signaling cascades by bridging other matrix molecules and tissue elements, affecting cell proliferation, adhesion, migration, and cytokine concentration. The aim of the study is to investigate the role of small leucine-rich proteoglycans in the pathogenesis of thin and thick human endometrium and their differences from normal endometrium in terms of fine structure properties. Normal, thin, and thick endometrial samples were collected, and small leucine-rich proteoglycans (SLRPs), decorin, lumican, biglycan, and fibromodulin immunoreactivities were comparatively analyzed immunohistochemically. The data were compared statistically. Moreover, ultrastructural differences among the groups were evaluated by transmission electron microscopy. The immunoreactivities of decorin, lumican, and biglycan were higher in the thin endometrial glandular epithelium and stroma compared to the normal and thick endometrium (p < .001). Fibromodulin immunoreactivity was also higher in the thin endometrial glandular epithelium than in the normal and thick endometrium (p < .001). However, there was no statistical difference in the stroma among the groups. Ultrastructural features were not profoundly different among cases. Telocytes, however, were not seen in the thin endometrium in contrast to normal and thin endometrial tissues. These findings suggest a possible role of changes in proteoglycan levels in the pathogenesis of thin endometrium.

薄子宫内膜,定义为子宫内膜厚度小于7 mm是辅助生殖治疗期间频繁取消胚胎移植或复发性植入失败的常见原因。小蛋白聚糖通过桥接其他基质分子和组织元素来调节细胞内信号级联,影响细胞增殖、粘附、迁移和细胞因子浓度。本研究的目的是研究富含亮氨酸的小蛋白聚糖在薄和厚人类子宫内膜发病机制中的作用,以及它们在精细结构特性方面与正常子宫内膜的差异。收集正常、薄和厚的子宫内膜样本,并用免疫组化方法比较分析富含亮氨酸的小蛋白多糖(SLRP)、decorin、lumican、biglycan和纤维调节蛋白的免疫反应性。对数据进行了统计比较。此外,通过透射电子显微镜评估各组之间的超微结构差异。与正常和厚内膜相比,薄内膜腺上皮和间质中decorin、lumican和biglycan的免疫反应性较高(p p
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引用次数: 0
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Ultrastructural Pathology
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