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Large Malignant Testicular/Paratesticular Tumors in Adolescence: Assessment of Gross Tumor Size in a Vulnerable Age Group. 青春期大型恶性睾丸/睾丸旁肿瘤:评估易受影响年龄组的肿瘤大小。
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-21
Ava G Stechschulte, Andrea C Bakker, Jasmine Steele, Sara O Vargas

Objective: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence.

Methods: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed.

Results: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups.

Conclusion: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.

目的: 我们假设,对腹股沟肿块缄默不语可能导致睾丸/睾丸旁恶性肿瘤在青春期早期至青春期晚期出现:我们假设,对腹股沟肿块缄默不语可能会导致睾丸/睾丸旁恶性肿瘤在青春期早期至青春期晚期出现:纳入1994-2023年期间在我院确诊的11-20岁患者的睾丸和睾丸旁恶性肿瘤(恶性生殖细胞瘤和横纹肌肉瘤)。记录临床病理特征,并进行统计学分析:结果:共发现 85 例病例。患者年龄从11岁到20岁不等(平均17岁,中位数16岁)。肿瘤最大尺寸从 0.8 厘米到 18.0 厘米不等(平均 4.4 厘米,中位数 3.5 厘米)。10个肿瘤(占病例的11.8%)≥10.0厘米。在 11-13 岁年龄组中,100%(3/3)的肿瘤≥10 厘米。11-13岁年龄组肿瘤≥10厘米的比例明显高于14-16岁年龄组:这组青少年睾丸和睾丸旁恶性肿瘤患者中,超大肿瘤(≥10厘米)的比例很高(11.8%)。虽然原因不明,而且很可能是多因素造成的,但这项研究表明,青少年,尤其是 11-13 岁年龄组的青少年,是一个易受影响的群体。
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引用次数: 0
Polydopamine Nanoparticles-Encapsulated Ferroptosis Inhibitor Ferstatin-1 Promotes GPX4 Expression by Down-Regulating NOX4 to Alleviate Myocardial Ischemia-Reperfusion Injury. 多多巴胺纳米粒子包裹的铁蛋白沉积抑制剂 Ferstatin-1 通过下调 NOX4 促进 GPX4 的表达,从而缓解心肌缺血再灌注损伤。
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01
Zhibo Hong, Jing Cui, Yu Chen

Objective: Polydopamine nanoparticles (PDA NPs) are a promising topic in the fields of drug delivery, tissue engineering, bioimaging, etc. The present study aims to explore the impact of PDA NPs carrying ferroptosis inhibitor ferstatin-1 (Fer-1) on myocardial ischemia-reperfusion injury (MIRI).

Methods: After establishment of a rat model of MIRI and PDA NPs, the rats were divided into 4 groups: model group, sham operation group, Fer-1 group, and nano+Fer-1 group (n=8). To detect the effect of PDA NPs encapsulating Fer-1 on ferroptosis in MIRI rats, we further set up NOX4 overexpression group (pc-NOX4 group), NOX4 inhibitor group (Fulvene-5 group), nano+Fer-1+pc-NOX4 group, and nano+Fer-1+Fulvene-5 group (n=8). A CCK-8 assay was conducted to assess cell viability and staining to detect cardiomyocyte apoptosis and observe myocardial infraction.

Results: PDA NPs loaded with Fer-1 were successfully prepared with good safety and biocompatibility. Administration of PDA NPs carrying Fer-1 notably alleviated myocardial injury and hindered the process of ferroptosis in MIRI rats when inducing downregulation of NOX4 expression. Additionally, overexpression of GPX4 significantly attenuated myocardial injury in MIRI rats. While Fer-1 was shown to inhibit the expression of NOX4, the NOX4 inhibitor Fulvene-5 greatly elevated GPX4 and FTH1 expression in cardiomyocytes, and down-regulated the content of Fe2+, especially in the nanometer+Fer-1+Fulvene-5 group.

Conclusion: With promising safety and biocompatibility, PDA NPs encapsulated Fer-1 decrease GPX4 and FTH1 expression by inhibiting the level of NOX4 in myocardial cells of MIRI rats, thereby suppressing ferroptosis of cardiomyocytes and alleviating myocardial injury.

目的:聚多巴胺纳米粒子(PDA NPs)在药物输送、组织工程、生物成像等领域是一个前景广阔的课题。本研究旨在探讨携带铁蛋白抑制剂铁司他丁-1(Fer-1)的 PDA NPs 对心肌缺血再灌注损伤(MIRI)的影响:建立大鼠心肌缺血再灌注损伤模型和PDA NPs后,将大鼠分为4组:模型组、假手术组、Fer-1组和纳米+Fer-1组(n=8)。为了检测包裹 Fer-1 的 PDA NPs 对 MIRI 大鼠铁突变的影响,我们进一步设置了 NOX4 过表达组(pc-NOX4 组)、NOX4 抑制剂组(Fulvene-5 组)、纳米+Fer-1+pc-NOX4 组和纳米+Fer-1+Fulvene-5 组(n=8)。用 CCK-8 法评估细胞活力,用染色法检测心肌细胞凋亡并观察心肌梗死:结果:含 Fer-1 的 PDA NPs 制备成功,具有良好的安全性和生物相容性。给 MIRI 大鼠注射含有 Fer-1 的 PDA NPs 能明显减轻心肌损伤,并在诱导 NOX4 表达下调的同时阻碍铁卟啉沉积过程。此外,过量表达 GPX4 能显著减轻 MIRI 大鼠的心肌损伤。Fer-1能抑制NOX4的表达,而NOX4抑制剂Fulvene-5能大大提高心肌细胞中GPX4和FTH1的表达,并下调Fe2+的含量,尤其是在纳米+Fer-1+Fulvene-5组中:封装 Fer-1 的 PDA NPs 具有良好的安全性和生物相容性,可通过抑制 MIRI 大鼠心肌细胞中 NOX4 的水平来降低 GPX4 和 FTH1 的表达,从而抑制心肌细胞的铁变态反应,减轻心肌损伤。
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引用次数: 0
Technical Note: Significant Positive Bias in Lower Concentrations but Negative Bias in Higher Concentrations in Testosterone Measurement Using Beckman Access Immunoassay Compared to a Liquid Chromatography-Tandem Mass Spectrometry Reference Method. 技术说明:与液相色谱-串联质谱参考方法相比,使用贝克曼通路免疫测定法测定睾酮时,低浓度存在明显的正偏差,而高浓度存在明显的负偏差。
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01
Amitava Dasgupta, Kelsey Woodard, Bheemraj Ramoo, Clinton Frazee, Uttam Garg

Objective: Testosterone is the principal male sex hormone and is secreted primarily by the testes. In most clinical laboratories testosterone is routinely measured for diagnosis of male hypogonadism or androgen excess in females using FDA approved immunoassays. We compared testosterone values measured by Beckman access immunoassay with those measured by a reference LC-MS/MS method.

Methods: Testosterone was measured in 36 patients using left over serum or plasma specimens by both Beckman immunoassay on the DXI 800 analyzer and a reference LC-MS/MS method.

Results: We observed overall significant negative bias of approximately 31.9 % when testosterone values obtained by the reference LC-MS/MS method were plotted in the x-axis and the corresponding testosterone values using the immunoassay in the y-axis, as regression equation was y=0.6887x+38.81 (n=36). The corresponding Deming regression was y=0.6639x+34.7163. However, in eight specimens with low testosterone concentrations, immunoassays significantly overestimated testosterone concentrations.

Conclusions: Immunoassays may underestimate the true testosterone concentration in males but overestimate in females with low testosterone concentration. Therefore, for diagnosis of hypogonadism in males and androgen excess in females, testosterone values obtained by Beckman Access immunoassay on the DXI 800 analyzer should be interpreted with caution.

目的:睾酮是男性的主要性激素,主要由睾丸分泌:睾酮是男性的主要性激素,主要由睾丸分泌。在大多数临床实验室中,睾酮是用于诊断男性性腺功能减退症或女性雄激素过多症的常规检测指标,使用的是美国食品及药物管理局(FDA)批准的免疫测定法。我们将贝克曼免疫测定法测得的睾酮值与 LC-MS/MS 参考方法测得的睾酮值进行了比较:使用 DXI 800 分析仪上的贝克曼免疫测定法和一种 LC-MS/MS 参考方法对 36 名患者的残留血清或血浆标本进行了睾酮测量:如果将 LC-MS/MS 参考方法获得的睾酮值绘制成 x 轴,将免疫测定法获得的相应睾酮值绘制成 y 轴,回归方程为 y=0.6887x+38.81 (n=36)。相应的戴明回归方程为 y=0.6639x+34.7163。然而,在 8 份睾酮浓度较低的标本中,免疫测定法明显高估了睾酮浓度:结论:免疫测定可能会低估男性睾酮的真实浓度,但会高估低睾酮浓度女性的睾酮浓度。因此,在诊断男性性腺功能减退症和女性雄激素过多症时,应谨慎解释贝克曼 Access 免疫测定法在 DXI 800 分析仪上获得的睾酮值。
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引用次数: 0
Fibrosis of the Intestines in Response to Foreign Objects: A Case Report. 异物引起的肠道纤维化:病例报告。
IF 1.1 4区 医学 Q4 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-03-01
Rita W J Hayes, Lance Van Truong, Nina Tatevian, Alexander Chirkov

Foreign body ingestion of sharp objects can be a striking feature of psychological dysfunction with high morbidity and mortality. While the phenomenon has been reported on, primarily from a psychiatric perspective, this report will present the effects of this behavior on the intestinal system from a pathology perspective. The report is of a 43-year-old female with a past medical history of foreign object ingestion, borderline personality disorder, depression, anxiety, and prior suicidality who passed away due to bowel obstruction. Review of her history revealed an eighteen-year history of repeated foreign body ingestion with multiple surgical interventions. A particularly remarkable aspect revealed through the surgical history is the nature of the complications. They begin in 2008 with bowel perforation due to a blunt object and continue to present with perforation in the early years but show a gradual change to adhesions and obstruction as the primary concern. Her final presentation to the hospital and cause of death was due to obstruction, not perforation, even though the foreign bodies were six knives. While this case is not the only known report of foreign body ingestion, the extensive timeline and frequency allow for an examination of the gradual progression of fibrosis and adhesions within the intestines and abdominal wall, which led to the obstruction and death despite being a protective factor against further perforation.This case was presented at the annual Association of Clinical Scientists meeting (April 2-4, Jacksonville, FL).

摄入尖锐物体的异物可能是心理功能障碍的一个显著特征,具有很高的发病率和死亡率。虽然这种现象主要是从精神病学的角度进行报道,但本报告将从病理学的角度介绍这种行为对肠道系统的影响。报告中的患者是一名 43 岁女性,既往病史为异物摄入、边缘型人格障碍、抑郁、焦虑和自杀,因肠梗阻去世。回顾她的病史,发现她有十八年的反复异物摄入史,并接受过多次手术治疗。手术史显示的一个特别之处是并发症的性质。这些并发症始于 2008 年的钝器导致的肠穿孔,最初几年仍以穿孔为主,但后来逐渐转变为以粘连和梗阻为主。尽管异物是六把刀,但她最终到医院就诊和死亡的原因是梗阻,而不是穿孔。虽然本病例不是唯一已知的异物摄入报告,但由于时间跨度大、发生频率高,因此可以对肠道和腹壁纤维化和粘连的逐渐发展进行研究,这导致了梗阻和死亡,尽管异物是防止进一步穿孔的保护因素。
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引用次数: 0
Long Non-Coding RNA FLG-AS1 Inhibits Cervical Cancer Progression through Negatively Modulating miR-147b. 长非编码 RNA FLG-AS1 通过负向调节 miR-147b 抑制宫颈癌进展
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01
Mengying Gao, Xixia Pang, Suna Ni, Zhixia Wei, Dandan Li

Objective: The study investigated the association between FLG-AS1 and cervical cancer prognosis and the interaction mechanism between FLG-AS1 and miR-147b in order to identify potential therapeutic targets for cervical cancer.

Methods: In this study, tissue samples and clinicopathological characteristics were obtained from 125 cervical cancer patients. FLG-AS1 expression levels in the samples were detected by polymerase chain reaction assay. CCK-8 and Transwell assays were used to evaluate FLG-AS1's impact on cervical cancer cell proliferation and metastasis. The mechanism of action of FLG-AS1 and miR-147b was probed by a dual luciferase reporter gene assay. The prognostic nature of FLG-AS1 in cervical cancer was explored by a series of statistical approaches.

Results: In cervical cancer cells and tissues, FLG-AS1 expression is markedly downregulated. FLG-AS1 inhibits the activities of cervical cancer cells by negatively regulating miR-147b expression. Patients with cervical cancer have a poor prognosis when FLG-AS1 expression is low.

Conclusion: FLG-AS1 may be considered as a novel cervical cancer prognostic biomarker candidate, which affects cancer cell progression by negatively regulating miR-147b.

研究目的该研究探讨了FLG-AS1与宫颈癌预后的关系以及FLG-AS1与miR-147b之间的相互作用机制,以确定宫颈癌的潜在治疗靶点:方法:本研究获得了125例宫颈癌患者的组织样本和临床病理特征。聚合酶链反应法检测样本中 FLG-AS1 的表达水平。CCK-8和Transwell试验用于评估FLG-AS1对宫颈癌细胞增殖和转移的影响。FLG-AS1和miR-147b的作用机制通过双荧光素酶报告基因实验进行了探究。通过一系列统计方法探讨了FLG-AS1在宫颈癌中的预后作用:结果:在宫颈癌细胞和组织中,FLG-AS1的表达明显下调。结果:在宫颈癌细胞和组织中,FLG-AS1 的表达明显下调,FLG-AS1 通过负调控 miR-147b 的表达来抑制宫颈癌细胞的活性。结论:FLG-AS1表达较低时,宫颈癌患者的预后较差:结论:FLG-AS1可被视为一种新型的宫颈癌预后生物标志候选物,它通过负向调节miR-147b来影响癌细胞的进展。
{"title":"Long Non-Coding RNA FLG-AS1 Inhibits Cervical Cancer Progression through Negatively Modulating miR-147b.","authors":"Mengying Gao, Xixia Pang, Suna Ni, Zhixia Wei, Dandan Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>The study investigated the association between FLG-AS1 and cervical cancer prognosis and the interaction mechanism between FLG-AS1 and miR-147b in order to identify potential therapeutic targets for cervical cancer.</p><p><strong>Methods: </strong>In this study, tissue samples and clinicopathological characteristics were obtained from 125 cervical cancer patients. FLG-AS1 expression levels in the samples were detected by polymerase chain reaction assay. CCK-8 and Transwell assays were used to evaluate FLG-AS1's impact on cervical cancer cell proliferation and metastasis. The mechanism of action of FLG-AS1 and miR-147b was probed by a dual luciferase reporter gene assay. The prognostic nature of FLG-AS1 in cervical cancer was explored by a series of statistical approaches.</p><p><strong>Results: </strong>In cervical cancer cells and tissues, FLG-AS1 expression is markedly downregulated. FLG-AS1 inhibits the activities of cervical cancer cells by negatively regulating miR-147b expression. Patients with cervical cancer have a poor prognosis when FLG-AS1 expression is low.</p><p><strong>Conclusion: </strong>FLG-AS1 may be considered as a novel cervical cancer prognostic biomarker candidate, which affects cancer cell progression by negatively regulating miR-147b.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156797","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: 0
Factors Influencing Blood Donation among Young Saudi Arabian Adults: A Cross-Sectional Study to Inform Donor Recruitment and Retention Programs. 影响沙特阿拉伯年轻成年人献血的因素:一项横断面研究,为献血者招募和保留计划提供信息。
IF 1.1 4区 医学 Q4 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-03-01
Fahd A Kuriri

Objective: Blood donation is critical in Saudi Arabia due to high rates of sickle cell disease and thalassemia. Recent trends show a decline in the number of blood donors, threatening blood supplies for medical treatments. This study aims to identify factors that influence blood donation decisions and behaviors among young Saudi Arabian adults to develop strategies to enhance donation rates.

Methods: A cross-sectional study was conducted with 407 university students in Riyadh Province (Shaqra, Riyadh City, Al-Majmaah and Al-Duwadimi) and occurred from December 2022 to May 2023, using convenience sampling. Data were collected via online questionnaires and analyzed using logistic regression.

Results: Findings revealed a significant gender disparity in donation rates with males more likely to donate. Knowledge gaps were prevalent, especially regarding eligibility criteria. Support for organ donation, prior experience of receiving blood, and high levels of self-determined motivation positively associated with donation likelihood. Conversely, amotivation was a strong negative predictor of donation.

Conclusion: This study highlights the importance of educational interventions to address misconceptions about blood donation and tailor campaigns to enhance donor motivation. Strategies focusing on these aspects could improve the donor pool and ensure a stable blood supply for patients with blood disorders in Saudi Arabia.

目的:由于镰状细胞病和地中海贫血的高发病率,献血在沙特阿拉伯至关重要。最近的趋势表明,献血者人数有所下降,威胁到医疗用血的供应。本研究旨在确定影响沙特阿拉伯年轻成年人献血决定和行为的因素,从而制定提高献血率的策略:本研究采用方便抽样法,于 2022 年 12 月至 2023 年 5 月对利雅得省(沙克拉、利雅得市、Al-Majmaah 和 Al-Duwadimi)的 407 名大学生进行了横断面研究。数据通过在线问卷收集,并采用逻辑回归法进行分析:调查结果显示,捐赠率存在明显的性别差异,男性更倾向于捐赠。知识差距普遍存在,尤其是在资格标准方面。对器官捐献的支持、先前接受血液的经验以及高水平的自我决定动机与捐献可能性呈正相关。相反,动机不足则是预测捐献的一个强烈的负面因素:本研究强调了教育干预的重要性,以消除人们对献血的误解,并为献血者量身定制宣传活动,以提高献血者的积极性。针对这些方面的策略可以改善献血者库,确保沙特阿拉伯血液病患者的稳定血液供应。
{"title":"Factors Influencing Blood Donation among Young Saudi Arabian Adults: A Cross-Sectional Study to Inform Donor Recruitment and Retention Programs.","authors":"Fahd A Kuriri","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Blood donation is critical in Saudi Arabia due to high rates of sickle cell disease and thalassemia. Recent trends show a decline in the number of blood donors, threatening blood supplies for medical treatments. This study aims to identify factors that influence blood donation decisions and behaviors among young Saudi Arabian adults to develop strategies to enhance donation rates.</p><p><strong>Methods: </strong>A cross-sectional study was conducted with 407 university students in Riyadh Province (Shaqra, Riyadh City, Al-Majmaah and Al-Duwadimi) and occurred from December 2022 to May 2023, using convenience sampling. Data were collected via online questionnaires and analyzed using logistic regression.</p><p><strong>Results: </strong>Findings revealed a significant gender disparity in donation rates with males more likely to donate. Knowledge gaps were prevalent, especially regarding eligibility criteria. Support for organ donation, prior experience of receiving blood, and high levels of self-determined motivation positively associated with donation likelihood. Conversely, amotivation was a strong negative predictor of donation.</p><p><strong>Conclusion: </strong>This study highlights the importance of educational interventions to address misconceptions about blood donation and tailor campaigns to enhance donor motivation. Strategies focusing on these aspects could improve the donor pool and ensure a stable blood supply for patients with blood disorders in Saudi Arabia.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158070","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: 0
Letter to the Editor: Effect of Guanosine Triphosphate on B Cell Characterization in U266 Cells. 致编辑的信:三磷酸鸟苷对 U266 细胞中 B 细胞特征的影响
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01
Tamar A Smith-Norowitz, Esther M Norowitz, Haram Abdelmajid, Stephan Kohlhoff
{"title":"<i>Letter to the Editor:</i> Effect of Guanosine Triphosphate on B Cell Characterization in U266 Cells.","authors":"Tamar A Smith-Norowitz, Esther M Norowitz, Haram Abdelmajid, Stephan Kohlhoff","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157955","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: 0
miR-4685-3p Alleviates Human Brain Microvascular Endothelial Cells Injury by Regulating MMP9. miR-4685-3p 通过调节 MMP9 减轻人脑微血管内皮细胞损伤
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01
Dan Ma, Yongting Lu, Hong Ye, Chunyan Li, Jie Zhang, Tian Hao Bao, Jianhong Han

Objective: Cerebral microbleeds (CMBs) are punctate hemorrhagic lesions within the brain parenchyma and are a classic manifestation of cerebral small vessel disease (CSVD). The primary objective of this study is to investigate the potential role of miR-4685-3p and underlying mechanisms by which miR-4685-3p modulates matrix metalloproteinase-9 (MMP9) in cerebral microvascular endothelial cell injury.

Methods: We employed high-throughput sequencing to screen for differentially expressed miRNAs in the peripheral blood of patients with CMBs and healthy controls. Employing lipopolysaccharide (LPS) to induce cellular damage, we aim to establish a model of human brain microvascular endothelial cells (hCMEC/D3) injury. We also had cells transfected with miR-4685-3p mimic and MMP9 overexpression plasmid. We utilized quantitative polymerase chain reaction (qPCR) to assess the expression levels of miR-4685-3p and performed Western blot analysis to examine MMP9 expression levels in the cells. We employed the CCK-8 assay, TUNEL assay, and tube formation assay to evaluate cellular viability, apoptotic rates, and angiogenic capabilities. Furthermore, dual-luciferase reporter assay analysis was conducted to confirm the relationship between miR-4685-3p and MMP9.

Results: The sequencing results indicated a downregulation of miR-4685-3p in the peripheral blood of patients with CMBs. Within the context of LPS-induced injury to hCMEC/D3 cells, miR-4685-3p exhibits reduced expression, whereas MMP9 expression levels are elevated. The elevation of miR-4685-3p expression levels attenuates LPS-induced cellular apoptosis and enhances the viability and tube-forming capacity of hCMEC/D3 cells. Concomitant transfection with MMP9 overexpression constructs effectively reversed the detrimental effects of LPS on hCMEC/D3 cell integrity. We further confirmed that miR-4685-3p overexpression directly targets MMP9, leading to negative regulation of MMP9 expression.

Conclusion: Upregulating miR-4685-3p, which targets the MMP9 axis, mitigated LPS-induced cerebral microvascular endothelial cell injury, potentially playing a protective role in the progression of CMBs.

目的:脑微出血(CMBs)是脑实质内的点状出血病变,是脑小血管病(CSVD)的典型表现。本研究的主要目的是探讨miR-4685-3p在脑微血管内皮细胞损伤中的潜在作用以及miR-4685-3p调节基质金属蛋白酶-9(MMP9)的潜在机制:方法:我们采用高通量测序技术筛选了CMB患者和健康对照者外周血中差异表达的miRNA。我们利用脂多糖(LPS)诱导细胞损伤,旨在建立人脑微血管内皮细胞(hCMEC/D3)损伤模型。我们还让细胞转染了 miR-4685-3p 模拟物和 MMP9 过表达质粒。我们利用定量聚合酶链反应(qPCR)来评估 miR-4685-3p 的表达水平,并进行 Western 印迹分析来检测细胞中 MMP9 的表达水平。我们采用 CCK-8 试验、TUNEL 试验和管形成试验来评估细胞活力、凋亡率和血管生成能力。此外,我们还进行了双荧光素酶报告分析,以确认 miR-4685-3p 与 MMP9 之间的关系:测序结果表明,在 CMB 患者的外周血中,miR-4685-3p 出现了下调。在 LPS 诱导的 hCMEC/D3 细胞损伤中,miR-4685-3p 的表达量减少,而 MMP9 的表达水平升高。miR-4685-3p 表达水平的升高减轻了 LPS 诱导的细胞凋亡,增强了 hCMEC/D3 细胞的活力和管形成能力。同时转染 MMP9 过表达构建体能有效逆转 LPS 对 hCMEC/D3 细胞完整性的不利影响。我们进一步证实,miR-4685-3p 的过表达直接靶向 MMP9,导致 MMP9 表达的负调控:结论:上调靶向 MMP9 轴的 miR-4685-3p 可减轻 LPS 诱导的脑微血管内皮细胞损伤,从而在 CMB 的进展过程中发挥潜在的保护作用。
{"title":"miR-4685-3p Alleviates Human Brain Microvascular Endothelial Cells Injury by Regulating MMP9.","authors":"Dan Ma, Yongting Lu, Hong Ye, Chunyan Li, Jie Zhang, Tian Hao Bao, Jianhong Han","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral microbleeds (CMBs) are punctate hemorrhagic lesions within the brain parenchyma and are a classic manifestation of cerebral small vessel disease (CSVD). The primary objective of this study is to investigate the potential role of miR-4685-3p and underlying mechanisms by which miR-4685-3p modulates matrix metalloproteinase-9 (MMP9) in cerebral microvascular endothelial cell injury.</p><p><strong>Methods: </strong>We employed high-throughput sequencing to screen for differentially expressed miRNAs in the peripheral blood of patients with CMBs and healthy controls. Employing lipopolysaccharide (LPS) to induce cellular damage, we aim to establish a model of human brain microvascular endothelial cells (hCMEC/D3) injury. We also had cells transfected with miR-4685-3p mimic and MMP9 overexpression plasmid. We utilized quantitative polymerase chain reaction (qPCR) to assess the expression levels of miR-4685-3p and performed Western blot analysis to examine MMP9 expression levels in the cells. We employed the CCK-8 assay, TUNEL assay, and tube formation assay to evaluate cellular viability, apoptotic rates, and angiogenic capabilities. Furthermore, dual-luciferase reporter assay analysis was conducted to confirm the relationship between miR-4685-3p and MMP9.</p><p><strong>Results: </strong>The sequencing results indicated a downregulation of miR-4685-3p in the peripheral blood of patients with CMBs. Within the context of LPS-induced injury to hCMEC/D3 cells, miR-4685-3p exhibits reduced expression, whereas MMP9 expression levels are elevated. The elevation of miR-4685-3p expression levels attenuates LPS-induced cellular apoptosis and enhances the viability and tube-forming capacity of hCMEC/D3 cells. Concomitant transfection with MMP9 overexpression constructs effectively reversed the detrimental effects of LPS on hCMEC/D3 cell integrity. We further confirmed that miR-4685-3p overexpression directly targets MMP9, leading to negative regulation of MMP9 expression.</p><p><strong>Conclusion: </strong>Upregulating miR-4685-3p, which targets the MMP9 axis, mitigated LPS-induced cerebral microvascular endothelial cell injury, potentially playing a protective role in the progression of CMBs.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156842","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: 0
Predictive Value of Serum Albumin, Iron, Ferritin, and Hepcidin for Antiviral Efficacy of IFNα Treatment in Patients with Chronic Hepatitis B. 慢性乙型肝炎患者血清白蛋白、铁、铁蛋白和肝磷脂对 IFNα 治疗抗病毒效果的预测价值
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01
Qian Liu, Futing Liu, Wanlu Duan, Yu Wei, Tingdong Zhou, Hao Zhang, Zhi Duan, Qiang Zhou, Qin Wang

Objective: Interferon-α (IFNα) therapy has been an integral part of the current treatment for hepatitis B virus (HBV) infection. However, the exact effect of IFNα antiviral therapy on liver function and iron metabolism in patients with chronic hepatitis B (CHB) remains unclear. Here, we investigated the characteristics of changes in liver function and iron metabolism indexes in patients with chronic hepatitis B before and after IFNα treatment. Additionally, we determined their predictive value for the therapeutic response of IFNα treatment.

Methods: In this study, 34 patients with CHB before and after IFNα treatment were enrolled. Serum levels of virological indicators, liver function, and iron metabolism markers were detected and analyzed in each patient. ROC curve analysis was performed to compare the predictive value of serum liver function and iron metabolism markers for the therapeutic response of IFN α treatment.

Results: A significant decrease in serum HBV DNA (P<0.001) and HBsAg (P<0.001) was observed before and after IFNα treatment. Compared to the patients before IFNα treatment, patients after IFNα treatment showed a significant increase in serum albumin (ALB) (P<0.05) and a significant decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P=0.003 and P=0.034). These findings suggested that the synthetic function of the liver was improved, and liver inflammation was alleviated. Serum HEPC and serum ferritin (SF) levels in patients after IFNα treatment were significantly higher (P<0.001, P<0.001); however, serum iron (SI) levels were significantly lower (P=0.005) than those in patients before IFNα treatment. These findings indicate that IFNα treatment regulated iron metabolism homeostasis in CHB patients. Combined liver function and iron metabolism markers, including ALB, SI, SF, and HEPC, had the highest predictive value for the therapeutic response of IFNα treatment for CHB.

Conclusion: IFNα treatment improved liver function and iron metabolism homeostasis in patients with CHB. Regular monitoring of serum ALB, SI, SF, and HEPC can help predict the therapeutic response of IFNα treatment for CHB.

目的:干扰素-α(IFNα)疗法是目前治疗乙型肝炎病毒(HBV)感染不可或缺的一部分。然而,IFNα抗病毒治疗对慢性乙型肝炎(CHB)患者肝功能和铁代谢的确切影响仍不清楚。在此,我们研究了 IFNα 治疗前后慢性乙型肝炎患者肝功能和铁代谢指标的变化特点。此外,我们还确定了它们对 IFNα 治疗反应的预测价值:本研究共纳入了 34 例 IFNα 治疗前后的慢性乙型肝炎患者。对每位患者的血清病毒学指标、肝功能和铁代谢指标水平进行检测和分析。对血清肝功能和铁代谢指标对 IFN α 治疗反应的预测价值进行了 ROC 曲线分析比较:血清HBV DNA明显下降(PPPP=0.003,P=0.034)。这些结果表明,肝脏的合成功能得到改善,肝脏炎症得到缓解。IFNα治疗后患者的血清HEPC和血清铁蛋白(SF)水平明显高于IFNα治疗前患者(PPP=0.005)。这些研究结果表明,IFNα治疗可调节慢性阻塞性肺病患者的铁代谢平衡。综合肝功能和铁代谢指标,包括ALB、SI、SF和HEPC,对IFNα治疗CHB的治疗反应具有最高的预测价值:结论:IFNα治疗可改善CHB患者的肝功能和铁代谢平衡。定期监测血清 ALB、SI、SF 和 HEPC 可以帮助预测 IFNα 治疗 CHB 的疗效。
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引用次数: 0
Expression of Glutathione Peroxidase4 in Patients with Esophageal Squamous Carcinoma and Its Impact on the Radiosensitivity of Esophageal Squamous Carcinoma. 食管鳞癌患者中谷胱甘肽过氧化物酶4的表达及其对食管鳞癌放射敏感性的影响
IF 0.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01
Chen Chen, Wendong Gu, Yingjie Shao, Panpan Zheng, Jingting Jiang

Objective: Glutathione peroxidase-4 (GPX4) is a member of Ferroptosis and lipid circulation. This study aims to investigate the expression of GPX4 in esophageal squamous cell carcinoma and its impact on radiosensitivity.

Method: Immunohistochemistry staining was used to detect GPX4 expression in 180 samples of ESCC tissues and adjacent tissues. We analyzed the relationship between GPX4 expression and ESCC clinical parameters. In vitro experiments were conducted using apoptosis assays and colony formation assays to investigate the effect of GPX4 on the radiosensitivity of ESCC cells. In vivo experiments were carried out using a nude mouse xenograft model to evaluate the impact of GPX4 on the radiosensitivity of ESCC.

Results: GPX4 expression was lower in adjacent tissues than tumor tissues. The expression of GPX4 was significantly associated with the pathological grade of ESCC. The overall survival time (OS) of ESCC patients with low GPX4 expression was significantly longer than that of patients with high GPX4 expression. GPX4 could be used as independent prognostic factors in patients with ESCC. In vivo experiments, silencing of GPX4 or using GPX4 inhibitors significantly inhibits the viability and colony formation of ESCC cells after radiation exposure while increasing intracellular reactive oxygen species (ROS) levels, and significantly suppresses the tumorigenic ability of ESCC cells in subcutaneous xenografts after radiation exposure.

Conclusion: GPX4 is highly expressed in ESCC, which has the potential value for prognostic assessment of ESCC. Silencing or inhibiting GPX4 can enhance the radiosensitivity of ESCC.

目的:谷胱甘肽过氧化物酶-4(GPX4谷胱甘肽过氧化物酶-4(GPX4)是铁氧化酶和脂质循环的成员之一。本研究旨在探讨 GPX4 在食管鳞状细胞癌中的表达及其对放射敏感性的影响:方法:采用免疫组化染色法检测 180 例 ESCC 组织和邻近组织样本中 GPX4 的表达。我们分析了 GPX4 表达与 ESCC 临床参数之间的关系。体外实验采用细胞凋亡测定和集落形成测定来研究 GPX4 对 ESCC 细胞放射敏感性的影响。使用裸鼠异种移植模型进行体内实验,评估 GPX4 对 ESCC 辐射敏感性的影响:结果:GPX4在邻近组织中的表达低于肿瘤组织。GPX4的表达与ESCC的病理分级显著相关。GPX4 低表达的 ESCC 患者的总生存时间(OS)明显长于 GPX4 高表达的患者。GPX4 可作为 ESCC 患者的独立预后因素。在体内实验中,沉默GPX4或使用GPX4抑制剂可明显抑制ESCC细胞在辐射照射后的存活率和集落形成,同时增加细胞内活性氧(ROS)水平,并可明显抑制ESCC细胞在辐射照射后皮下异种移植的致瘤能力:结论:GPX4 在 ESCC 中高表达,具有评估 ESCC 预后的潜在价值。沉默或抑制 GPX4 可增强 ESCC 的放射敏感性。
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Annals of clinical and laboratory science
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