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Rabbit-based experimental model for scalp reimplantation: advancing microsurgical training and translational research. 兔头皮再植实验模型:推进显微外科训练与转化研究。
Pub Date : 2025-04-28 eCollection Date: 2025-01-01 DOI: 10.1590/acb403725
Rui Sergio Monteiro de Barros, José Maciel Caldas Dos Reis, Deivid Ramos Dos Santos, Vitor Nagai Yamaki, Renan Kleber Costa Teixeira, André Lopes Valente

Purpose: To develop an experimental model of microsurgical scalp reimplantation in rabbits.

Methods: Ten male albino New Zealand rabbits (Oryctolagus cuniculus) were scalped and subjected to scalp reimplantation. The rabbits' scalp regions, including their ears, were surgically amputated. Based on a previous anatomical study, the superficial temporal artery and the central auricular vein were chosen for microanastomosis. Data on the morphometric parameters (vessel weight and caliber), surgical procedure (surgical time and number of stitches), and surgical recovery parameters (venous return, patency, and necrosis) were collected for up to 30 days postoperatively (PO) using a research protocol.

Results: Morphometric and surgical recovery parameters did not significantly differ in our sample. No animals died during the intraoperative period. Three animals were euthanized because they developed partial or total scalp necrosis. The venous return was impaired from three to ten days PO, with spontaneous regression after this period, which significantly improved (p = 0.02) after 14 days PO. Superficial necrosis was observed starting at two days PO with complete resolution by day 21 PO (p <0.01).

Conclusion: The rabbit provides a realistic biological model for training scalp reimplantation with high fidelity to human vascular structures.

目的:建立兔头皮显微外科再植实验模型。方法:选取10只雄性白化新西兰兔(Oryctolagus cuuniculus)进行头皮再植。这些兔子的头皮区域,包括耳朵,都被手术切除了。根据以往的解剖学研究,我们选择颞浅动脉和耳中央静脉进行显微吻合。使用研究方案收集了术后30天(PO)的形态学参数(血管重量和口径)、手术程序(手术时间和针数)和手术恢复参数(静脉回流、通畅和坏死)的数据。结果:形态学和手术恢复参数在我们的样本中没有显著差异。术中无动物死亡。三只动物因为部分或全部头皮坏死而被安乐死。术后第3 ~ 10天静脉回流受损,术后自发性消退,术后第14天静脉回流明显改善(p = 0.02)。从第2天开始观察到表面坏死,到第21天完全消退(p)结论:家兔为训练头皮再植提供了一个真实的生物学模型,具有高保真度的人体血管结构。
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引用次数: 0
Hirudin inhibits ferroptosis to improve renal fibrosis by targeting the STAT3/NLRP3 signaling pathway. 水蛭素通过靶向STAT3/NLRP3信号通路抑制铁下垂改善肾纤维化。
Pub Date : 2025-04-28 eCollection Date: 2025-01-01 DOI: 10.1590/acb403325
Fang Lan, Chunli Long, Huimin Huang, Yongxiang Xie, Wei Shi

Purpose: To reveal the role and underlying mechanism of hirudin in renal fibrosis.

Methods: The unilateral ureteral obstruction (UUO) rat model and ferroptosis activator RSL3-induced human kidney proximal tubular epithelial cells (HK-2) were established. Hematoxylin-eosin staining, commercial kits, and immunohistochemistry were used to assess the effect of hirudin on renal function and renal fibrosis. Cell counting kit-8 assay was employed to test cell viability. Ferroptosis indicator levels were detected using commercial kits. The protein levels were examined by Western blot. The STAT3 activator colivelin was introduced to verify the role of the STAT3/NLRP3 signaling pathway in ferroptosis.

Results: Hirudin alleviated renal injury and improved renal fibrosis in UUO rats. The cell viability of RSL3-treated HK-2 cells was increased after hirudin treatment. In the model group, GPX4, SLC7A11, and glutathione expression decreased, while malondialdehyde and iron content levels increased, indicating that ferroptosis was activated. Besides, p-STAT3 and NLRP3 protein levels were also upregulated. However, hirudin treatment reversed these changes. When the STAT3 activator colivelin was added, the effect of hirudin was altered.

Conclusion: Hirudin improved renal fibrosis by inhibiting ferroptosis via the STAT3/NLRP3 signaling pathway.

目的:探讨水蛭素在肾纤维化中的作用及其机制。方法:建立单侧输尿管梗阻(UUO)大鼠模型和上吊铁激活剂rsl3诱导的人肾近端小管上皮细胞(HK-2)。采用苏木精-伊红染色、商业试剂盒和免疫组织化学评估水蛭素对肾功能和肾纤维化的影响。细胞计数试剂盒-8法检测细胞活力。使用商用试剂盒检测下垂铁指标水平。Western blot检测蛋白水平。我们引入STAT3激活因子colivelin来验证STAT3/NLRP3信号通路在铁下垂中的作用。结果:水蛭素减轻UUO大鼠肾损伤,改善肾纤维化。水蛭素处理后,rsl3处理的HK-2细胞活力增加。模型组GPX4、SLC7A11、谷胱甘肽表达降低,丙二醛、铁含量升高,提示铁下沉被激活。此外,p-STAT3和NLRP3蛋白水平也上调。然而,水蛭素治疗逆转了这些变化。当加入STAT3激活剂colcolvelin时,水蛭素的作用发生改变。结论:水蛭素通过STAT3/NLRP3信号通路抑制铁下垂,改善肾纤维化。
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引用次数: 0
Re-stricture after buccal mucosal graft urethroplasty: a systematic review and meta-analysis. 口腔粘膜移植尿道成形术后再狭窄:系统回顾和荟萃分析。
IF 1.3 Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb403525
Gustavo Bono Yoshikawa, Gabriella Giandotti Gomar, Giovanna Ceccatto Gadens, Beatriz França Zanetti Saes, Maria Eduarda Andrade Galiciolli, Meire Ellen Pereira, Quelen Iane Garlet, Cláudia Sirlene Oliveira

Purpose: To determine risk factors for re-stricture after buccal mucosal graft urethroplasty (BMGU) through a systematic review and meta-analysis.

Methods: Following PRISMA guidelines, we collected data from PubMed, Scientific Electronic Library Online (SciELO), and Web of Science databases. The eligibility criteria included studies with male patients over 18 years old with urethral stricture recurrence after BMGU.

Results: We retrieved 646 papers from three electronic databases. Records that did not meet the eligibility criteria and duplicates were excluded, resulting in 14 papers (3,240 patients) that underwent qualitative analysis, from which nine papers were suitable for meta-analysis. The meta-analysis identified diabetes mellitus (relative risk - RR: 1.58 [95% confidence interval - 95%CI 1.02-2.46];p = 0.04), penile/peno-bulbar site (RR: 1.57 [95%CI 1.04-2.37]; p = 0.03), and stricture size higher than 7 cm (RR: 4.13 [95%CI 2.42-7.04]; p 0.00001) as a predictive factor of re-stricture.

Conclusions: These findings may improve understanding the risk factors for this type of urethroplasty and help surgical decisions. For a more effective analysis, larger and better-distributed study groups and cohorts are needed in the future to clarify whether the combination of a previous disease and the urethroplasty etiology may impact a recurrence-free outcome after stricture correction.

目的:通过系统回顾和荟萃分析,确定颊粘膜移植尿道成形术(BMGU)后再狭窄的危险因素。方法:按照PRISMA指南,我们从PubMed、SciELO和Web of Science数据库中收集数据。入选标准包括18岁以上男性BMGU术后尿道狭窄复发患者。结果:从3个电子数据库中检索到论文646篇。排除了不符合入选标准和重复的记录,有14篇论文(3240例患者)进行了定性分析,其中9篇论文适合进行meta分析。meta分析确定糖尿病(相对危险度- RR: 1.58[95%可信区间- 95% ci 1.02-2.46];p = 0.04)、阴茎/阴茎球部位(RR: 1.57 [95% ci 1.04-2.37];p = 0.03),狭窄尺寸大于7 cm (RR: 4.13 [95%CI 2.42-7.04];P 0.00001)作为再狭窄的预测因素。结论:这些发现有助于了解此类尿道成形术的危险因素,并有助于手术决策。为了进行更有效的分析,未来需要更大、分布更好的研究小组和队列来阐明既往疾病和尿道成形术病因的结合是否会影响狭窄矫正后无复发的结果。
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引用次数: 0
Immediate and late effects of supraphysiological doses of nandrolone decanoate on the testis of rats. 超生理剂量癸酸诺龙对大鼠睾丸的即时和后期影响。
Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb402925
Bruno Felix-Patricio, Roger Gaspar Marchon, Bianca Martins Gregório, Diogo Benchimol De Souza

Purpose: To investigate the effects of supraphysiologic doses of nandrolone decanoate on the testicular morphology of rats and if these effects could be transitory or permanent.

Methods: Twenty-five male rats were divided in four groups. C28 and C40 were control rats killed with 28 and 40 weeks old, respectively; and T28 and T40 were treated with nandrolone decanoate (10 mg/kg) and killed immediately after the treatment (T28) or 12 weeks after the end of treatment (T40). The testis weight and volume were measured, and the seminiferous tubule area and epithelium height were assessed by histomorphometric methods.

Results: The seminiferous tubules area and epithelium height of group T28 were reduced in comparison to C28. Group T40 showed reduced testicular weight and volume, as well as seminiferous tubule area and epithelium height in comparison to C40.

Conclusion: The use of nandrolone decanoate promotes major structural modifications on the testes of rats. These modifications are even worse 12 weeks after ending the use of the anabolic androgenic steroid.

目的:探讨超生理剂量癸酸诺龙对大鼠睾丸形态的影响及这种影响是暂时性的还是永久性的。方法:25只雄性大鼠分为4组。C28和C40分别为28周龄和40周龄处死的对照大鼠;T28和T40分别给予十酸诺龙(10 mg/kg)治疗,治疗后立即(T28)或治疗结束后12周(T40)处死。测量睾丸重量和体积,用组织形态学方法测定精小管面积和上皮高度。结果:T28组精小管面积和上皮高度较C28组明显减少。与C40组相比,T40组睾丸重量、体积、精小管面积和上皮高度均减少。结论:癸酸诺龙可促进大鼠睾丸结构的改变。在停止使用合成代谢雄激素类固醇12周后,这些变化甚至更糟。
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引用次数: 0
A new eggshell-derived calcium phosphate bioceramic for tissue engineering: cytotoxicity and histomorphometric study. 一种用于组织工程的新型蛋壳来源的磷酸钙生物陶瓷:细胞毒性和组织形态学研究。
Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb402625
Conrado Dias do Nascimento Neto, Laisa Kindely Ramos de Oliveira, Amy Brian Costa E Silva, Patrícia Roccon Bianchi, André Gustavo de Sousa Galdino, Daniela Nascimento Silva

Purpose: To evaluate cytotoxicity and tissue repair of a new chicken eggshell-derived bioceramic (hydroxyapatite/dicalcium phosphate anhydrous-HA/DCPA).

Methods: Cytotoxicity was evaluated in fibroblasts (L cell, L-929) by MTT test. Tissue repair of HA/DCPA was compared to HA/β-TCP bioceramic (Maxresorb-MXR). Two critical-sized bone defects (CSDs) were drilled in the calvarial of 24 Wistar rats and filled with one of the biomaterials. The animals were euthanized after 30, 60, and 90 days, and bone specimens were examined by histomorphometric analyses, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The percentages of newly formed bone, connective tissue, remaining biomaterial, and total tissue repair area were compared between groups using Student's t-test and analysis of variance (p ≤ 0.05).

Results: HA/DCPA did not exhibit any cytotoxicity. CSDs contained newly formed bone from the defect margins and from ossification centers interspersed throughout the biomaterials. At 30 days, HA/DCPA group had a significantly larger total tissue repair area than MXR group (p = 0.047). No differences were observed between groups regarding variables studied (p > 0.05).

Conclusion: HA/DCPA is non-cytotoxic. This cement promoted new bone formation and tissue filling of the entire defect area with degree of biomaterial degradation similar to HA/β-TCP, proving to be equally suitable and successful for bone regeneration.

目的:评价一种新型蛋壳生物陶瓷(羟基磷灰石/无水磷酸二钙- ha /DCPA)的细胞毒性和组织修复作用。方法:采用MTT法测定成纤维细胞(L细胞,L-929)的细胞毒性。比较HA/DCPA与HA/β-TCP生物陶瓷(Maxresorb-MXR)的组织修复效果。在24只Wistar大鼠颅骨上钻取两个临界大小的骨缺损(CSDs),并用其中一种生物材料填充。分别在30,60和90天后对动物实施安乐死,并通过组织形态学分析,扫描电子显微镜和能量色散x射线光谱学检查骨标本。新成骨百分率、结缔组织百分率、剩余生物材料百分率、组织修复总面积百分率比较采用Student’st检验和方差分析(p≤0.05)。结果:HA/DCPA无细胞毒性。csd包含来自缺损边缘和骨化中心的新形成的骨,这些骨分布在整个生物材料中。30 d时,HA/DCPA组的组织修复面积显著大于MXR组(p = 0.047)。各组间研究变量无差异(p < 0.05)。结论:HA/DCPA无细胞毒性。该骨水泥促进了整个缺损区域的新骨形成和组织填充,生物材料降解程度与HA/β-TCP相似,同样适用于骨再生并取得了成功。
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引用次数: 0
Type I and type III collagen immunoexpression in rabbit skin biopsy samples treated with rosuvastatin gel and autologous platelet-rich plasma. 用洛伐他汀凝胶和自体富血小板血浆处理兔皮肤活检样本的 I 型和 III 型胶原蛋白免疫表达。
Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb402725
Cristoffer da Silva Santana, Maria Rosa Santos Breda, Yuri Ferreira Vicentini, Sérgio Alexandre Alcantara Dos Santos, Luis Antonio Justulin, Anthony Cesar de Souza Castilho, Gisele Alborghetti Nai, Cecília Laposy Santarém

Purpose: To evaluate whether the joint use of autologous platelet-rich plasma (aPRP) and rosuvastatin (RSV) in biopsies of dermal wounds induced in rabbits results in an additive effect on the immunoexpression of collagens type I and III, optimizing the healing process and increasing collagen production during the proliferative phase of healing to improve the quality of tissue repair.

Methods: Thirty-two biopsy samples from eight clinically healthy adult male New Zealand rabbits were used. They were treated with aPRP, RSV, or aPRP + RSV and analyzed zero, three, seven, ten, and 14 days post wound induction.

Results: Type I collagen immunoexpression was significantly higher in wounds treated with aPRP when compared to the control group. This study demonstrated that type III collagen is predominant during the proliferation phase of the healing process, highlighting its critical role in tissue repair and regeneration.

Conclusion: The association of aPRP and RSV in wound treatment may have an additive effect in the immunoexpression of type III collagen and can thus be used as an alternative in tissue repair and collagen formation, optimizing the healing process.

目的:评价自体富血小板血浆(aPRP)和瑞舒伐他汀(RSV)联合应用于兔皮肤创面活检是否对I型和III型胶原的免疫表达产生叠加效应,优化愈合过程,增加愈合增殖期胶原的生成,提高组织修复质量。方法:选取临床健康成年雄性新西兰兔8只,活检标本32份。分别给予aPRP、RSV或aPRP + RSV治疗,并在创面诱导后0、3、7、10和14天进行分析。结果:与对照组相比,aPRP治疗创面I型胶原免疫表达明显升高。本研究表明,III型胶原蛋白在愈合过程的增殖阶段占主导地位,突出了其在组织修复和再生中的关键作用。结论:aPRP和RSV在创面治疗中的联合作用可能对III型胶原的免疫表达具有叠加效应,可作为组织修复和胶原形成的替代,优化愈合过程。
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引用次数: 0
Comparison between biliary plastic stents with and without application of silver nanoparticles: an in-vitro study of the biofilm formation. 使用和不使用纳米银的胆道塑料支架的比较:生物膜形成的体外研究。
Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb402825
Victor Kalil Flumignan, Marcelo de Palma Sircili, Marcia Regina Franzolin, Ana Marisa Chudzinski Tavassi, Lígia Garcia Germano, Ana Vitória Dos Santos Souza, Nicole Fernandes Silva, Newton Kiyoshi Fukumasu, Raphaela Marques Dos Anjos, Jose Pinhata Otoch, Everson Luiz de Almeida Artifon

Purpose: Plastic biliary stents are a cost-effective treatment for biliary obstruction. Unfortunately, they have low patency, related to intraluminal biofilm formation. Silver nanoparticles (AgNPs) have been increasingly used in biomedicine because of its antibacterial properties. This study aimed to compare biofilm formation on stents with and without silver nanoparticle coatings when in contact with different bacterial culture medium.

Methods: Different types of silver coatings were tested on plastic biliary stents. Two groups of stents were analyzed: one group with various types of silver nanoparticle coatings, and a negative control group with no coating. The stents were placed in different bacterial culture media and assessed for biofilm formation. Analysis was performed using confocal microscopy and direct colony-forming unit (CFU/cm2).

Results: Quantitative analysis showed promising results with C16 coating, as Escherichia coli ATCC and Pseudomonas aeruginosa ATCC exhibited reduced growth in the AgNP-coated group (p < 0.05). However, when mixed samples, including clinical strains and Staphylococcus aureus, were tested, the AgNP coating did not inhibit bacterial growth.

Conclusion: AgNP-coated stents are effective against certain strains, such as E. coli ATCC and P. aeruginosa. Further research is needed to explore potential improvements in the coating mechanism.

目的:塑料胆道支架是治疗胆道梗阻的一种经济有效的方法。不幸的是,它们的通畅度较低,这与腔内生物膜的形成有关。银纳米颗粒因其抗菌性能在生物医学领域的应用日益广泛。本研究旨在比较有银纳米颗粒涂层和没有银纳米颗粒涂层的支架与不同细菌培养基接触时生物膜的形成情况。方法:对不同类型的银膜在塑料胆道支架上的应用进行了试验。对两组支架进行分析:一组有不同类型的纳米银涂层,另一组没有涂层。将支架放置在不同的细菌培养基中并评估生物膜的形成。使用共聚焦显微镜和直接菌落形成单位(CFU/cm2)进行分析。结果:定量分析显示,C16包被组的大肠杆菌ATCC和铜绿假单胞菌ATCC在agnp包被组的生长速度下降(p < 0.05)。然而,当测试混合样品时,包括临床菌株和金黄色葡萄球菌,AgNP涂层没有抑制细菌的生长。结论:agnp包被支架对大肠杆菌ATCC和铜绿假单胞菌均有较好的抑制作用。需要进一步的研究来探索涂层机理的潜在改进。
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引用次数: 0
Epidemiological profile trends and cost of sickle cell disease in Brazil from 2008 to 2022. 2008 至 2022 年巴西镰状细胞病的流行病学概况趋势和费用。
Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb403025
Luiza Telles, Paulo Henrique Moreira Melo, Gabriele Eckerdt Lech, Luana Baptistele Dornelas, Natália Zaneti Sampaio, Ayla Gerk, Madeleine Carroll, Cristina Camargo

Purpose: This study aimed to evaluate the epidemiological profile trends and economic impact of sickle cell disease (SCD) in Brazil from 2008 to 2022, focusing on incidence, mortality, and healthcare costs.

Methods: A cross-sectional analysis was conducted using data from the Fundação Oswaldo Cruz's platform, Plataforma de Ciência de Dados Aplicada à Saúde, encompassing hospitalizations related to SCD from January 2008 to December 2022. The International Classification of Diseases codes for SCD were used to retrieve data on incidence, mortality, procedures performed, and healthcare costs.

Results: The study included 151,535 hospitalizations for SCD, with 69.92% associated with SCD crises and 22.48% without crises. The mean annual hospitalizations were higher for crises (6,883.06) compared to those without crises (2,221.12). Mortality rates were significantly higher for patients hospitalized with crises compared to those without crises (p < 0.001). The economic impact of SCD was substantial, with annual costs exceeding 413 million USD.

Conclusion: This study revealed a significant burden of SCD in Brazil, characterized by high hospitalization rates, particularly among younger patients, and elevated mortality rates associated with crises. Prospective studies and public health interventions are warranted to address SCD and mitigate its impact on public health.

目的:本研究旨在评估2008年至2022年巴西镰状细胞病(SCD)的流行病学概况、趋势和经济影响,重点关注发病率、死亡率和医疗成本。方法:使用funda o Oswaldo Cruz’s platform (platform aforma de Ciência de Dados applications)的数据进行横断面分析,包括2008年1月至2022年12月与SCD相关的住院病例。使用SCD的国际疾病分类代码检索有关发病率、死亡率、执行的程序和医疗费用的数据。结果:本研究共纳入151535例SCD住院患者,其中69.92%伴有SCD危像,22.48%无危像。危机患者的平均年住院率(6,883.06)高于无危机患者(2,221.12)。危象住院患者的死亡率明显高于无危象住院患者(p < 0.001)。SCD的经济影响是巨大的,每年的成本超过4.13亿美元。结论:这项研究揭示了巴西SCD的重大负担,其特点是住院率高,特别是在年轻患者中,以及与危重相关的死亡率升高。有必要进行前瞻性研究和公共卫生干预,以解决SCD并减轻其对公共卫生的影响。
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引用次数: 0
Chemoprotective effect of nimbolide against N-methyl-N-nitrosourea induced gastric cancer via alteration of apoptosis and NF-κB signaling pathway. nimbolide通过改变细胞凋亡和NF-κB信号通路对n -甲基-n -亚硝基脲诱导胃癌的化学保护作用。
Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb402125
Yizhong Gu, Binguo Liu, Xiaoting Xia, Chunlei Luo, Yi Ren

Purpose: Gastric cancer (GC) ranks as the third most common cause of cancer related mortality and as the fifth most frequently diagnosed cancer globally. Less than 30% of people with GC survive for more than five years.

Methods: Nimbolide has been shown to have anticancer, anti-inflammatory, antiparasitic, and antioxidant properties. The current investigation showed the anticancer effect of nimbolide against N-methyl-N-nitrosourea (MNU) induced GC in rats. Rats were given MNU (100 mg/kg) orally to induce GC and received the oral administration of nimbolide (10, 20 and 40 mg/kg). The different biochemical parameters were estimated.

Results: Nimbolide significantly (p < 0.001) altered the level of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cytochrome P450, cytochrome B5 and histone deacetylase (HDAC) activity. Nimbolide treatment significantly (p < 0.001) altered the level of antioxidant parameters like superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA); cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6; inflammatory parameters viz., cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the serum and stomach tissue. Nimbolide considerably altered (p < 0.001) the level of apoptosis parameters (Bcl-2, Bax and caspase-3), and the mRNA expression of VCAM-1, ICAM-1, TNF-α, IL-1β, IL-6, MCP-1, TLR4 and NF-κB.

Conclusion: Nimbolide treatment considerably altered the GC against MNU induced GC via alteration of apoptosis and NF-κB signaling pathway.

目的:胃癌(GC)是全球癌症相关死亡的第三大常见原因,也是第五大最常诊断的癌症。不到30%的胃癌患者能存活5年以上。方法:Nimbolide已被证明具有抗癌、抗炎、抗寄生虫和抗氧化的特性。本研究显示了nimbolide对n -甲基-n -亚硝基脲(MNU)诱导的大鼠胃癌的抗癌作用。大鼠口服MNU (100 mg/kg)诱导GC,同时口服nimbolide(10、20、40 mg/kg)。对不同生化参数进行了估计。结果:Nimbolide显著(p < 0.001)改变了乳酸脱氢酶(LDH)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、细胞色素P450、细胞色素B5和组蛋白去乙酰化酶(HDAC)活性。Nimbolide处理显著(p < 0.001)改变了抗氧化参数如超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)、丙二醛(MDA)的水平;肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-2、IL-6等细胞因子;血清和胃组织炎症参数环氧化酶-2 (COX-2)、前列腺素E2 (PGE2)、血管内皮生长因子(VEGF)、活化B细胞核因子κB轻链增强因子(NF-κB)。Nimbolide显著改变了凋亡参数Bcl-2、Bax和caspase-3的水平(p < 0.001),以及VCAM-1、ICAM-1、TNF-α、IL-1β、IL-6、MCP-1、TLR4和NF-κB的mRNA表达。结论:Nimbolide通过改变细胞凋亡和NF-κB信号通路,明显改变了MNU诱导的GC。
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引用次数: 0
Investigation of the effect of thymoquinone and doxorubicin on the EGFR/FOXP3 signaling pathway in OVCAR3 human ovarian adenocarcinoma cells. 百里醌和阿霉素对OVCAR3人卵巢腺癌细胞EGFR/FOXP3信号通路影响的研究
Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.1590/acb401725
İlhan Özdemir, Ayfer Şanli Aktaş, Mehmet Cudi Tuncer

Purpose: To investigate the cytotoxic and apoptotic effects of the combination of doxorubicin (Dox) and thymoquinone (TQ) on ovarian adenocarcinoma cells (OVCAR3) via the EGFR/FOXP3 signaling pathway.

Methods: We used human OVCAR3 and human skin keratinocyte cells (HaCaT). Different concentrations of TQ and Dox were applied to the cells for 24, 48, and 72 hours, and the cytotoxicity level was determined via the MTT method. Expression levels of EGFR/FOXP3 for cell proliferation and apoptosis were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot analysis. The colony counting was performed after DAPI staining, and the effect on cell proliferation was determined.

Results: Cytotoxicity was found to be highest with TQ and Dox treatments, and cell migration was prevented, especially in the group that received combined TQ and Dox treatment. Moreover, using RT-qPCR analysis, activity in the EGFR and FOXP3 pathway was found to be downregulated the most with TQ, and the amount of protein decreased with TQ and Dox.

Conclusions: The findings showed that the greatest cytotoxic effect and the most apoptosis occurred during TQ treatment. Additionally, it was determined that a significant decrease in EGFR and FOXP3 levels occurred with the application of TQ and Dox.

目的:探讨多柔比星(Dox)联合百里醌(TQ)通过EGFR/FOXP3信号通路对卵巢腺癌细胞(OVCAR3)的细胞毒性和凋亡作用。方法:采用人OVCAR3和人皮肤角质形成细胞(HaCaT)。不同浓度的TQ和Dox分别作用于细胞24、48和72小时,通过MTT法测定细胞毒性水平。采用定量逆转录聚合酶链反应(RT-qPCR)和Western blot检测EGFR/FOXP3在细胞增殖和凋亡中的表达水平。DAPI染色后进行菌落计数,测定对细胞增殖的影响。结果:TQ和Dox治疗组细胞毒性最高,且细胞迁移受阻,尤其是TQ和Dox联合治疗组。此外,通过RT-qPCR分析,发现EGFR和FOXP3通路的活性在TQ中下调最多,蛋白量随着TQ和Dox而减少。结论:TQ治疗期间细胞毒作用最大,细胞凋亡最多。此外,我们还发现,使用TQ和Dox后,EGFR和FOXP3水平显著降低。
{"title":"Investigation of the effect of thymoquinone and doxorubicin on the EGFR/FOXP3 signaling pathway in OVCAR3 human ovarian adenocarcinoma cells.","authors":"İlhan Özdemir, Ayfer Şanli Aktaş, Mehmet Cudi Tuncer","doi":"10.1590/acb401725","DOIUrl":"10.1590/acb401725","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the cytotoxic and apoptotic effects of the combination of doxorubicin (Dox) and thymoquinone (TQ) on ovarian adenocarcinoma cells (OVCAR3) via the EGFR/FOXP3 signaling pathway.</p><p><strong>Methods: </strong>We used human OVCAR3 and human skin keratinocyte cells (HaCaT). Different concentrations of TQ and Dox were applied to the cells for 24, 48, and 72 hours, and the cytotoxicity level was determined via the MTT method. Expression levels of EGFR/FOXP3 for cell proliferation and apoptosis were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot analysis. The colony counting was performed after DAPI staining, and the effect on cell proliferation was determined.</p><p><strong>Results: </strong>Cytotoxicity was found to be highest with TQ and Dox treatments, and cell migration was prevented, especially in the group that received combined TQ and Dox treatment. Moreover, using RT-qPCR analysis, activity in the EGFR and FOXP3 pathway was found to be downregulated the most with TQ, and the amount of protein decreased with TQ and Dox.</p><p><strong>Conclusions: </strong>The findings showed that the greatest cytotoxic effect and the most apoptosis occurred during TQ treatment. Additionally, it was determined that a significant decrease in EGFR and FOXP3 levels occurred with the application of TQ and Dox.</p>","PeriodicalId":93850,"journal":{"name":"Acta cirurgica brasileira","volume":"40 ","pages":"e401725"},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Acta cirurgica brasileira
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