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Long-term intake of aspartame-induced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger P53-dependent apoptosis in a mouse model 在小鼠模型中,长期摄入阿斯巴甜诱导的心血管毒性反映在组织化学参数的改变,引起氧化应激,并触发p53依赖性细胞凋亡
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-10-17 DOI: 10.1111/iep.12458
Hojat Anbara, Mehdi Kian, Gholam-Hossein Darya, Mohammad Taghi Sheibani

Aspartame (ASP) is probably the best known artificial sugar substitute that is used widely in food. Many experimental studies have reported the toxicity of long-term administration of ASP in various organ tissues. However, there is little evidence available about the nature and mechanisms of the adverse effects of long-term consumption of ASP on the cardiovascular system. This study was conducted to evaluate the possible effects of ASP on heart tissue. For this study 36 mature male mice were divided into one control group and three groups which received respectively 40 mg/kg, 80 mg/kg and 160 mg/kg ASP orally, for 90 days. ASP at the doses of 80 and 160 mg/kg increased the serum content of malondialdehyde (MDA), but decreased serum nitric oxide (NO), creatine kinase (CK) and CK-MB, as well as blood superoxide dismutase (SOD) levels. Serum level of total anti-oxidant capacity (TAC) in blood was also reduced in serum at the dose of 80 mg/kg. Histochemical staining, including Periodic acid-Schiff, Masson's trichrome and Verhoeff-van Gieson staining, indicated that ASP at doses of 80 and 160 mg/kg reduced glycogen deposition and decreased the number of collagen and elastic fibres in the cardiac tissue. The cardiac expression of pro-apoptotic genes, including P53, Bax, Bcl-2 and Caspase-3, was modulated at the dose of 160 mg/kg. Moreover, transcription of Caspase-3 was up-regulated at the dose of 80 mg/kg. In conclusion, long-term consumption of ASP any higher than the acceptable daily intake (40 mg/kg) appears to act by promoting oxidative stress, has the potential to alter both histopathological and biochemical parameters, and induces P53-dependent apoptosis in cardiac tissue.

阿斯巴甜(ASP)可能是最著名的人造糖替代品,广泛用于食品中。许多实验研究报道了长期服用ASP对多种器官组织的毒性。然而,关于长期食用ASP对心血管系统的不良影响的性质和机制,几乎没有证据。本研究旨在评价ASP对心脏组织可能产生的影响。本研究将36只成年雄性小鼠分为1个对照组和3个组,分别口服40 mg/kg、80 mg/kg和160 mg/kg ASP,为期90 d。80和160 mg/kg剂量的ASP提高了血清丙二醛(MDA)含量,降低了血清一氧化氮(NO)、肌酸激酶(CK)和CK- mb以及超氧化物歧化酶(SOD)水平。在80mg /kg剂量下,血清总抗氧化能力(TAC)水平也降低。组织化学染色,包括周期性酸-希夫染色、马松三色染色和verhoefff -van Gieson染色,表明80和160 mg/kg剂量的ASP减少了糖原沉积,减少了心脏组织中胶原和弹性纤维的数量。160 mg/kg剂量可调节心肌促凋亡基因P53、Bax、Bcl-2和Caspase-3的表达。此外,80mg /kg剂量下Caspase-3的转录上调。综上所述,长期摄入高于可接受日摄入量(40 mg/kg)的ASP似乎通过促进氧化应激起作用,有可能改变组织病理学和生化参数,并诱导心肌组织p53依赖性细胞凋亡。
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引用次数: 1
Skin fibrosis associated with keloid, scleroderma and Jorge Lobo's disease (lacaziosis): An immuno-histochemical study 皮肤纤维化与瘢痕疙瘩、硬皮病和Jorge Lobo病(lacaziosis)相关:一项免疫组织化学研究
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1111/iep.12456
Wagner Luiz Tafuri, Thaise Yumie Tomokane, Ana Maria Gonçalves Silva, Luciane Kanashiro-Galo, David Miichael Mosser, Juarez Antonio Simões Quaresma, Carla Pagliari, Mirian N. Sotto

Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-β. Higher expression of vimentin in comparison to α-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of α-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-β was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role.

纤维化是许多组织和器官遭受慢性损伤的常见病理生理反应。尽管瘢痕疙瘩、缺乏症和局限性硬皮病的病因不同,但在这三种疾病的发病机制中,纤维化的过程都存在于其他个体的临床和组织学特征之外。在这三种慢性皮肤炎症性疾病的20个样本中分别研究了纤维化。采用免疫组化方法研究α-平滑肌肌动蛋白(α-SMA)和波形蛋白细胞骨架抗原CD31、CD34、Ki67、p16的存在;CD105、CD163、CD206和FOXP3抗原;中心纤维化细胞因子TGF-β。与α-SMA相比,波形蛋白在三种病变类型中的表达均较高。血管内皮细胞CD31和cd34阳性遍布网状真皮。Ki67在硬皮病中表达低且几乎不表达。p16阳性表达水平高于ki67,在瘢痕疙瘩的网状真皮、硬皮病的胶原束和lacaziosis肉芽肿的外层均可见到p16阳性表达。α-肌动蛋白阳性细胞和罕见的CD34阳性细胞的存在,主要在瘢痕疙瘩中观察到,可能与p16抗原的高表达有关,p16抗原是细胞衰老的一个指标。所有病变类型均可见FOXP3低表达。在瘢痕疙瘩和硬皮病中,cd105阳性细胞主要出现在与外膜密切接触的维管周围组织中,而在lacaziosis中,cd105阳性细胞主要与外肉芽肿层胶原沉积结合。我们没有发现CD163或cd206阳性细胞高度参与纤维化过程。TGF-β仅在瘢痕疙瘩和lacazosis病变中表现显著。总之,我们认为在所有三种研究疾病中,vimentin是纤维化过程的主要肌成纤维细胞一般标记物,而内皮-间充质转化(EndoMT)、间充质干细胞(MSCs)和M2巨噬细胞可能不起重要作用。
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引用次数: 0
Circular RNAs hsa_circ_0001438 and hsa_circ_0000417 are downregulated and upregulated, respectively, in hepatocellular carcinoma 环状rna hsa_circ_0001438和hsa_circ_0000417分别在肝细胞癌中下调和上调
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-09-24 DOI: 10.1111/iep.12457
Sachiko Imanishi, Shoko Nagata, Toshitsugu Fujita, Hodaka Fujii

Hepatocellular carcinoma (HCC) is the most predominant type of liver cancer and is frequently fatal. Alpha-fetoprotein, alpha-fetoprotein-L3, and protein induced by vitamin K absence or antagonist-II are used as biomarkers to diagnose HCC. However, these biomarkers are not highly specific, especially for early-stage HCC diagnosis; therefore, more specific biomarkers are needed. Recently, circular RNA (circRNA) biomarkers have been used to diagnose several intractable diseases. In this study, we sought to identify circRNA biomarkers for the specific diagnosis of HCC. To this end, we compared the expression levels of circRNAs in primary HCC and normal tissues using publicly available RNA-seq data. Our analysis revealed that the expression levels of eight circRNAs were altered in primary HCC tissues compared with normal tissues. To confirm our findings, we examined the expression levels of selected circRNAs in HCC cell lines and normal hepatocytes. The expression level of hsa_circ_0001438, a circRNA that was downregulated in primary HCC, was lower in poorly and well-differentiated HCC cell lines than in normal hepatocytes. By contrast, the expression level of hsa_circ_0000417, which was increased in primary HCC, was strongly upregulated in a well-differentiated HCC cell line compared with normal hepatocytes. Thus, hsa_circ_0001438 and hsa_circ_0000417 might be potential biomarkers for the specific diagnosis of HCC. The experimental strategy described here, using publicly available RNA-seq data, is a useful and cost-effective method of identifying circRNA biomarkers.

肝细胞癌(HCC)是最主要的肝癌类型,通常是致命的。甲胎蛋白、甲胎蛋白- l3和维生素K缺失或拮抗剂- ii诱导的蛋白被用作诊断HCC的生物标志物。然而,这些生物标志物并不是高度特异性的,特别是对于早期HCC的诊断;因此,需要更特异的生物标志物。最近,环状RNA (circRNA)生物标志物已被用于诊断几种难治性疾病。在这项研究中,我们试图确定用于HCC特异性诊断的circRNA生物标志物。为此,我们使用公开的RNA-seq数据比较了原发性HCC和正常组织中circRNAs的表达水平。我们的分析显示,与正常组织相比,原发性HCC组织中8种circrna的表达水平发生了改变。为了证实我们的发现,我们检测了肝癌细胞系和正常肝细胞中选定的环状rna的表达水平。hsa_circ_0001438是一种在原发性HCC中下调的circRNA,其在低分化和高分化HCC细胞系中的表达水平低于正常肝细胞。相比之下,hsa_circ_0000417的表达水平在原发性HCC中升高,而在分化良好的HCC细胞系中,与正常肝细胞相比,表达水平明显上调。因此,hsa_circ_0001438和hsa_circ_0000417可能是HCC特异性诊断的潜在生物标志物。本文描述的实验策略使用公开可用的RNA-seq数据,是鉴定circRNA生物标志物的一种有用且具有成本效益的方法。
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引用次数: 1
Adenosquamous Carcinoma of Ascending Colon: Where an Unseen is Seen 升结肠腺鳞癌:见未见者
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-09-19 DOI: 10.33696/pathology.3.031
Prachi, H. Aiyer
The frequency of adenosquamous carcinoma of the colon is <0.1% [1-3]. The first case of colorectal adenosquamous carcinoma was reported by Herxheimer in 1907 and was described as a tumor with both adenocarcinoma and squamous cell carcinoma components. These tumors have a greater potential to metastasize as compared to conventional adenocarcinoma of the colon. Adenosquamous carcinoma, located in the ascending colon is rare and has a poor prognosis. Thus, early detection of adenosquamous carcinoma is important and treatment of choice is surgical resection followed by adjuvant chemotherapy. An adenosquamous carcinoma in the lower gastrointestinal tract is a rare malignancy with a frequency of 0.020.06% [4].
结肠腺鳞癌的发生率<0.1%[1-3]。1907年,Herxheimer报道了首例结直肠腺鳞癌,并将其描述为一种兼具腺癌和鳞状细胞癌成分的肿瘤。与传统的结肠腺癌相比,这些肿瘤有更大的转移可能性。位于升结肠的腺鳞癌是一种罕见且预后差的疾病。因此,早期发现腺鳞癌是重要的,治疗的选择是手术切除后辅助化疗。下胃肠道腺鳞癌是一种罕见的恶性肿瘤,发病率为0.020.06%[4]。
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引用次数: 0
The Proliferative Changes of Renal Afferent Arteriolar Walls and Renin-Angiotensin-Aldosterone System Inhibitors 肾传入小动脉壁增生性变化及肾素-血管紧张素-醛固酮系统抑制剂
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-09-19 DOI: 10.33696/pathology.3.035
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引用次数: 0
Newborns’ Hearing Health Associated with Infectious Diseases in Primary Healthcare Infectious Diseases and Neonatal Hearing Screening 初级卫生保健中新生儿听力健康与传染病的关系
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-09-19 DOI: 10.33696/pathology.3.034
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引用次数: 0
Can Artificial Intelligence Help? 人工智能能帮上忙吗?
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-09-19 DOI: 10.33696/pathology.3.033
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引用次数: 1
Cancer Stem Cells, Together with Mesenchymal Stem Cells and Other Cooperative Cells, Govern the Initiation and Development of Cancer 癌症干细胞,与间充质干细胞和其他协同细胞一起,控制癌症的发生和发展
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-09-19 DOI: 10.33696/pathology.3.032
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引用次数: 0
Morphophysiological alterations in fruit-eating bats after oral exposure to deltamethrin 口服溴氰菊酯后食果蝙蝠的形态生理变化。
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-09-04 DOI: 10.1111/iep.12455
Jerusa Maria Oliveira, Suellen Silva Condessa, Ana Luiza Fonseca Destro, Graziela Domingues Almeida Lima, Marli do Carmo Cupertino, Silvia Almeida Cardoso, Mariella Bontempo Freitas, Leandro Licursi de Oliveira

Deltamethrin (DTM) is a synthetic pyrethroid widely used in the cultivation and management of several crops due to its insecticidal action. Application to crops of pyrethroids such as DTM can result in the exposure of water and fruit consumed by fruit bats having a high pyrethroid content which may be harmful. Therefore the objective of this study was to evaluate the effects of short-term oral exposure of the fruit-eating bats (Artibeus lituratus) to two concentrations of DTM (0.02 and 0.04 mg/kg of papaya) on histopathology of the intestine, liver and kidney. The intestine of the animals exposed to both concentrations showed inflammatory infiltrate, degeneration, necrosis and goblet cell hyperplasia as the most frequent pathologies. Besides, the acid mucins showed an increase in the frequency of non-viable cells. The liver showed hepatocyte vacuolizatio and nuclear enlargement, as well as inflammatory infiltrate and steatosis. The kidneys of the exposed animals showed and inflammatory infiltrate, benign nephrosclerosis, vacuolization and necrosis. Also, DTM reduced nitric oxide synthesis, decreased glomerular diameter and increased glycogen percentage in the proximal tubules. Our results suggest that acute exposure to DTM at low concentrations has the potential to induce pronounced histopathological changes in vital organs, such as intestine, liver and kidney of fruit-eating bats.

溴氰菊酯(DTM)是一种合成拟除虫菊酯,由于其杀虫作用,被广泛用于多种作物的种植和管理。在作物上施用拟除虫菊酯,如DTM,会导致具有高拟除虫菊酯含量的果蝙蝠消耗的水和水果暴露在外,这可能是有害的。因此,本研究的目的是评估食果蝙蝠短期口服暴露于两种浓度的DTM(0.02和0.04)的影响 mg/kg木瓜)对肠、肝和肾组织病理学的影响。暴露于这两种浓度的动物的肠道显示炎症浸润、变性、坏死和杯状细胞增生是最常见的病理。此外,酸性粘蛋白显示不活细胞的频率增加。肝脏显示肝细胞空泡化和细胞核增大,以及炎症浸润和脂肪变性。暴露动物的肾脏出现炎症浸润、良性肾硬化、空泡化和坏死。此外,DTM减少了一氧化氮的合成,降低了肾小球直径,增加了近端小管中的糖原百分比。我们的研究结果表明,急性暴露于低浓度的DTM有可能在重要器官中诱导显著的组织病理学变化,如食果蝙蝠的肠道、肝脏和肾脏。
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引用次数: 2
Evaluation of the Relationship between Capillaroscopic Symptoms and the Severity of Systemic Lupus Erythematous 评价毛细血管镜下症状与系统性红斑狼疮严重程度的关系
IF 3 4区 医学 Q3 PATHOLOGY Pub Date : 2022-08-30 DOI: 10.33696/pathology.3.037
F. Shirani, Leila Barahimi
Objectives: Use of imaging tools can detect some specific pathological changes associated with systemic lupus erythematous (SLE). This study aimed to investigate the relationship between capillaroscopic symptoms and the severity of SLE.Methods: This was a cross-sectional study carried out on 56 patients with SLE undergoing capillaroscopy referred to Rasool-e Akram hospital in Tehran in 2018. Capillaroscopy findings were assessed according to demographic characteristics and duration of disease.Results: All patients had at least one positive finding related to capillaroscopy. Regarding capillaroscopic findings, abnormal microvascular structure in 37.5%, decreased vascular density in 78.6%, enlarged cap loop in 32.1%, microhemorrhage in 16.1% and neoangiogenesis in 25.0% were observed. The results revealed higher vascular density loss in women and higher neoangiogenesis in affected men and higher rate of abnormal microvascular structure at older ages and microhemorrhage at younger ages. Direct relationship was also found between duration of disease and microhemorrhage.Conclusion: Almost all patients with SLE undergoing capillaroscopy had at least one pathophysiological change in the capillary bed. The most common pathophysiological change was decreased vascular density, abnormal microvascular structure and capillary loop enlargement.
目的:利用影像学工具可以发现与系统性红斑狼疮(SLE)相关的一些特定病理改变。本研究旨在探讨毛细血管镜下症状与SLE严重程度之间的关系。方法:这是一项横断面研究,对2018年在德黑兰Rasool-e Akram医院接受毛细血管镜检查的56例SLE患者进行了研究。根据人口统计学特征和疾病持续时间评估毛细血管镜检查结果。结果:所有患者至少有一项与毛细管镜检查相关的阳性发现。微血管镜检查结果:微血管结构异常占37.5%,血管密度下降占78.6%,帽环增大占32.1%,微出血占16.1%,新生血管生成占25.0%。结果显示,女性的血管密度损失更高,男性的新生血管生成更高,老年人微血管结构异常率更高,年轻时微血管出血率更高。病程与微出血也有直接关系。结论:几乎所有接受毛细血管镜检查的SLE患者毛细血管床至少有一种病理生理改变。最常见的病理生理变化是血管密度降低、微血管结构异常和毛细血管袢增大。
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引用次数: 0
期刊
International Journal of Experimental Pathology
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