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Propofol suppresses breast cancer invasion: An in vitro three-dimensional cell invasion model with microfluidic technology. 异丙酚抑制乳腺癌侵袭:微流控技术体外三维细胞侵袭模型
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 Epub Date: 2025-12-11 DOI: 10.32725/jab.2025.019
Zhitong Wan, Haoyue Lyu, Yuting Luo, Tong Liu, Xiaoyu Peng, Yijing Zhang, Yuan Li

The fundamental aspect of breast cancer metastasis is the infiltration of malignant cells, which can be blocked by propofol, a widely utilized anesthetic in clinical settings, as recent studies reporting. However, research utilizing three-dimensional invasion models in vitro has not been documented. This study created a microfluidic chip model utilizing type I collagen (Col1), integrating delayed dynamic imaging and several fluorescence labeling approaches to objectively assess the inhibitory effect of propofol on breast cancer cell MDA-MB-231 invasion. Research indicates that MDA-MB-231 cells demonstrate collective invasion behavior, with their invasive capacity reliant on the degradation of the extracellular matrix (ECM) facilitated by matrix metalloproteinases (MMPs): both the invasion distance and cell count diminish as matrix hardness (collagen concentration 1-2.5 mg/ml) increases, while they augment with extended culture duration (1-5 days). Subsequent research has demonstrated that propofol (12.5-50 μg/ml) can reduce both the invasion distance and quantity of MDA-MB-231 cells in a dose-dependent manner, potentially linked to the down-regulation of MMP-2/MMP-9 and the up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. This paper presents novel experimental evidence that propofol inhibits the invasion of breast cancer cells, and establishes a straightforward and quantitative medication evaluation platform, offering a methodological reference for the screening and mechanistic investigation of tumor microenvironment regulators.

乳腺癌转移的基本方面是恶性细胞的浸润,这可以被异丙酚阻断,异丙酚是一种广泛应用于临床环境的麻醉剂,最近的研究报道。然而,利用体外三维侵袭模型的研究尚未有文献记载。本研究利用I型胶原蛋白(Col1)构建微流控芯片模型,整合延迟动态成像和多种荧光标记方法,客观评价异丙酚对乳腺癌细胞MDA-MB-231侵袭的抑制作用。研究表明,MDA-MB-231细胞表现出集体侵袭行为,其侵袭能力依赖于基质金属蛋白酶(MMPs)对细胞外基质(ECM)的降解:随着基质硬度(胶原浓度1-2.5 mg/ml)的增加,侵袭距离和细胞数量都减少,而随着培养时间的延长(1-5天),侵袭距离和细胞数量增加。随后的研究表明,异丙酚(12.5 ~ 50 μg/ml)能以剂量依赖的方式减少MDA-MB-231细胞的侵袭距离和数量,可能与下调MMP-2/MMP-9和上调组织金属蛋白酶抑制剂(TIMP-1)表达有关。本文提出了异丙酚抑制乳腺癌细胞侵袭的新实验证据,建立了直观、定量的用药评价平台,为肿瘤微环境调节剂的筛选和机制研究提供了方法学参考。
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引用次数: 0
Relationship between interleukin-37 genetic polymorphisms and HBV-related liver disease in a Chinese Han cohort. 中国汉族人群中白细胞介素-37基因多态性与hbv相关肝病的关系
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 Epub Date: 2025-10-30 DOI: 10.32725/jab.2025.017
Ping Fang, Ping Meng, Lijun Du, Hui Li, Rong Wang, Juan Zhao, Decheng Cai

Hepatitis B virus (HBV)-related liver disease is an inflammatory-associated disease, with diverse clinical phenotypes ranging from asymptomatic HBV carriers to hepatocellular carcinoma. Interleukin-37 (IL-37), a cytokine that effectively inhibits innate and adaptive immunity, has powerful anti-inflammatory and anti-tumor effects. Several single nucleotide polymorphisms (SNPs) in the IL37 gene are genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression. However, different ethnic groups may have different allele frequencies and linkage disequilibrium structures. The effect of SNPs in IL37 on HBV infection and its relationship with different clinical outcomes have not been clarified among the Han people in southern China. Based on in silico functional prediction and previously reported in the literature to be potentially associated with diseases, we screened seven potentially functional SNPs (rs3811046, rs3811047, rs2723176, rs2723186, rs4611652, rs4392270, and rs4241122) located in the IL37 genomic region and 3-kb upstream and downstream of the gene body. 1,582 subjects were included in the study, including 747 patients with HBV-related liver disease, 405 patients who cleared HBV, and 430 healthy controls. The seven SNPs were genotyped using the SNaPshot SNP assay, and co-dominant, dominant, and recessive models were used to explore the association of each SNP with HBV infection and clinical outcomes after HBV infection. The rs4241122 demonstrated a significant association with both HBV infection and its clinical outcomes, with the GG genotype identified as an independent protective factor for spontaneous clearance of HBV. The rs2723186 and rs4392270 were also significantly associated with HBV clearance under specific genetic models. Furthermore, rs3811046 and rs3811047 were correlated with the progression of liver abnormalities following HBV infection. Our data suggests that SNPs at the IL37 locus are associated with susceptibility to HBV infection and clinical outcomes after HBV infection.

乙型肝炎病毒(HBV)相关肝病是一种炎症相关疾病,具有多种临床表型,从无症状HBV携带者到肝细胞癌。白细胞介素-37 (IL-37)是一种有效抑制先天免疫和适应性免疫的细胞因子,具有强大的抗炎和抗肿瘤作用。IL37基因中的几个单核苷酸多态性(snp)是HBV感染和HBV介导的肝脏疾病进展的遗传预测危险因素。然而,不同的族群可能具有不同的等位基因频率和连锁不平衡结构。在中国南方汉族人群中,IL37 snp对HBV感染的影响及其与不同临床结局的关系尚未明确。基于计算机功能预测和先前文献报道的可能与疾病相关的信息,我们筛选了位于IL37基因组区和基因体上下游3kb的7个潜在功能snp (rs3811046、rs3811047、rs2723176、rs2723186、rs4611652、rs4392270和rs4241122)。1582名受试者纳入研究,包括747名HBV相关肝病患者,405名HBV清除患者和430名健康对照。使用SNaPshot SNP测定法对这7个SNP进行基因分型,并使用共显性、显性和隐性模型来探索每个SNP与HBV感染和HBV感染后临床结局的关系。rs4241122与HBV感染及其临床结果有显著相关性,GG基因型被确定为HBV自发清除的独立保护因子。在特定的遗传模型下,rs2723186和rs4392270也与HBV清除显著相关。此外,rs3811046和rs3811047与HBV感染后肝脏异常的进展相关。我们的数据表明,IL37位点的snp与HBV感染的易感性和HBV感染后的临床结果相关。
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引用次数: 0
Exosomes from LPS-stimulated macrophages alleviate neuroinflammatory responses by reducing pyroptosis in systemic lipopolysaccharide-induced mice. 脂多糖刺激的巨噬细胞外泌体通过减少系统性脂多糖诱导小鼠的焦亡来减轻神经炎症反应。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 Epub Date: 2025-12-08 DOI: 10.32725/jab.2025.018
Tao Ying, Zhezhe Sun

Central nervous system (CNS) inflammation occurs in cognitive dysfunction, but the underlying mechanisms remain unclear. The newly discovered pattern of cell death in recent years is called pyroptosis, which is distinguished from apoptosis and necrosis, and is mainly dependent on caspase-1 mediated inflammatory response. Stem-derived exosomes have immunomodulatory and immunosuppressive effects. In the present study, we aimed to investigate the exosomes (Ex) secreted by lipopolysaccharide (LPS)-stimulated macrophages (LPS-Ex) to attenuate the neuroinflammatory response caused by systemic LPS stimulation by attenuating pyroptosis. We studied lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6 mice by behavioral testing, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Western blotting, and other methods. We found that LPS-Ex can reduce the level of inflammatory factors, down-regulate the pyroptosis pathway and the inflammatory pathway of NF-κB, and improve the inflammatory response of neurological function in mice. The conclusion is that LPS-Ex relieves neuroinflammation by reducing pyroptosis. It can be used as a novel therapeutic strategy for neuroprotection and functional recovery in the onset of central nervous system inflammation.

中枢神经系统(CNS)炎症发生在认知功能障碍中,但其潜在机制尚不清楚。近年来新发现的细胞死亡模式称为焦亡,它区别于细胞凋亡和坏死,主要依赖于caspase-1介导的炎症反应。茎源性外泌体具有免疫调节和免疫抑制作用。在本研究中,我们旨在研究脂多糖(LPS)刺激的巨噬细胞(LPS-Ex)分泌的外泌体(Ex)通过减轻焦亡来减轻全身LPS刺激引起的神经炎症反应。通过行为学测试、免疫荧光、酶联免疫吸附试验(ELISA)、Western blotting等方法研究脂多糖(LPS)对C57BL/6小鼠认知功能损伤和神经炎症的影响。我们发现LPS-Ex可以降低炎症因子水平,下调焦亡通路和NF-κB炎症通路,改善小鼠神经功能的炎症反应。结论:LPS-Ex通过减少焦亡来减轻神经炎症。它可以作为中枢神经系统炎症发作时神经保护和功能恢复的一种新的治疗策略。
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引用次数: 0
Elevated plasma levels of cell-free mtDNA are associated with acute rejection following heart transplantation. 血浆游离mtDNA水平升高与心脏移植后急性排斥反应有关。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-01 Epub Date: 2025-09-25 DOI: 10.32725/jab.2025.014
Dana Dlouha, Kristyna Janouskova, Sarka Chytilova, Jevgenija Vymetalova, Marianna Lukasova, Sarka Novakova, Eva Rohlova, Jaroslav A Hubacek

Acute rejection (AR) following heart transplantation (HTx) is a common complication, especially in the early post-HTx period. Mitochondrial DNA (mtDNA), released into circulation from stressed mitochondria, mimics ongoing immune activation and facilitates the release of pro-inflammatory substances. Our study aimed to assess cell-free mtDNA levels to identify early indicators of acute rejection progression. The absolute concentration of cf-mtDNA (cp/μl) was measured in 77 adult patients using quantitative polymerase chain reaction. Blood samples (n = 300) were collected before their corresponding biopsy according to the timeline within the first year post-HTx. The median cf-mtDNA levels in samples with confirmed AR (n = 57) was higher compared to samples without diagnosed rejection (n = 210; Padj < 0.01). When acute cellular (ACR; n = 39) and antibody-mediated rejection (AMR; n = 18) were analyzed separately, only AMR demonstrated higher levels compared to samples without diagnosed rejection (Padj = 0.02). The highest cf-mtDNA levels were detected in samples collected during early post-HTx complications compared to samples without rejection and AR samples (for both Padj < 0.0001). Both ACR and AMR were observed throughout the one-year period, with the majority (3rd quartile) occurring during the first 200 days post-HTx. Post-HTx complications, such as graft dysfunction or acute kidney injury, were observed within the first 11 days, with the majority (71.4%) occurring within 5 days post-HTx. The presence of AR, and specifically AMR, is associated with elevated levels of cf-mtDNA. The increase in plasma cf-mtDNA levels strongly reflects the occurrence of early complications following HTx.

急性排斥反应(AR)是心脏移植术后常见的并发症,尤其是在心脏移植后的早期。线粒体DNA (mtDNA)从应激线粒体释放到循环中,模拟正在进行的免疫激活并促进促炎物质的释放。我们的研究旨在评估无细胞mtDNA水平,以确定急性排斥进展的早期指标。采用定量聚合酶链反应法测定了77例成年患者体内cf-mtDNA的绝对浓度(cp/μl)。根据htx术后第一年的时间线,在相应的活检前采集血样(n = 300)。确诊AR的样本(n = 57)中位cf-mtDNA水平高于未确诊排斥反应的样本(n = 210; Padj < 0.01)。当分别分析急性细胞性排斥反应(ACR, n = 39)和抗体介导的排斥反应(AMR, n = 18)时,只有AMR的水平高于未诊断排斥反应的样本(Padj = 0.02)。与没有排斥反应的样本和AR样本相比,htx并发症早期收集的样本中检测到的cf-mtDNA水平最高(Padj均< 0.0001)。ACR和AMR在一年的时间内都被观察到,大多数(第三四分位数)发生在htx后的前200天。htx术后并发症,如移植物功能障碍或急性肾损伤,在前11天内观察到,大多数(71.4%)发生在htx术后5天内。AR的存在,特别是AMR,与cf-mtDNA水平升高有关。血浆cf-mtDNA水平的升高强烈反映了HTx术后早期并发症的发生。
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引用次数: 0
Epidemiology of late postoperative bleeding in OSA-related tonsil surgery: a multicentric retrospective study. asa相关扁桃体手术术后晚期出血的流行病学:一项多中心回顾性研究。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-01 Epub Date: 2025-09-29 DOI: 10.32725/jab.2025.016
Jan Vodicka, Martin Chovanec, Milan Urik, Bretislav Gal, Rami Katra, Petr Skopek, Veronika Glumbikova, Anna Svejdova, Zdenek Knizek, Jan Kolin, Hana Dolezalova, Libor Sychra, Patrik Bursa, Lenka Jetmarova, Silvia Berkova, Pavel Strejcek, Josef Hajek, Tomas Kostlivy, David Slouka

Introduction: Tonsil-related procedures are considered fundamental and effective in the surgical treatment of obstructive sleep apnea (OSA). The range of techniques includes intratonsillar approaches, such as tonsillotomy (TT), as well as extracapsular procedures, such as tonsillectomy (TE) and uvulopalatopharyngoplasty (UPPP). Patients undergoing these procedures span all age groups, from children to seniors.

Methods: This multicentric retrospective study, conducted between 2014 and 2018, analysed data from 3,498 patients who underwent bilateral TT, TE, or UPPP for OSA or ronchopathy. The cohort included 2,221 men (63.49%) and 1,277 women (36.51%). Of these, 2,808 patients (80.27%) underwent TT, 226 (6.46%) underwent TE, and 464 (13.26%) underwent UPPP.

Results: Late postoperative haemorrhage (LPOH) occurrence was significantly associated with the type of surgery (p < 0.0001) and the hospital where the procedure was performed (p < 0.0001). The incidence of LPOH in the TT group ranged from 0% to 5.88% across hospitals (p = 0.0068); whereas in the TE and UPPP groups, rates ranged from 0% to 33.33% (p = 0.0413 and p = 0.0409, respectively). The occurrence of repetitive bleeding was not influenced by treatment choice (readmission vs. outpatient care, observation vs. surgical revision, general vs. local anaesthesia). The severity of bleeding in all three groups was not affected by age and gender. The use of anticoagulants negatively impacted LPOH severity (p = 0.0166) in the UPPP group. No deaths occurred in our sample; however, three cases of severe postoperative bleeding (grade "D") were observed.

Conclusion: Late postoperative haemorrhage remains a serious complication of tonsil-related surgery with the potential for life-threatening outcomes. The marked variability in bleeding incidence between surgical techniques and departments highlights the need for standardised perioperative protocols. Although no fatalities occurred, the occurrence of severe cases underlines the importance of vigilant postoperative monitoring. In our OSA cohort, tonsillotomy showed favourable safety, and recent evidence suggests it may represent a valuable alternative also in recurrent tonsillitis, warranting further research.

扁桃体相关手术被认为是阻塞性睡眠呼吸暂停(OSA)手术治疗的基础和有效方法。技术范围包括扁桃体内入路,如扁桃体切开术(TT),以及囊外手术,如扁桃体切除术(TE)和悬雍垂腭咽成形术(UPPP)。接受这些手术的病人涵盖了从儿童到老年人的所有年龄组。方法:这项多中心回顾性研究于2014年至2018年进行,分析了3498名因OSA或脊柱疾病接受双侧TT、TE或UPPP治疗的患者的数据。该队列包括2221名男性(63.49%)和1277名女性(36.51%)。其中,2808例患者(80.27%)接受了TT, 226例(6.46%)接受了TE, 464例(13.26%)接受了UPPP。结果:术后晚期出血(LPOH)的发生与手术类型(p < 0.0001)和手术医院(p < 0.0001)显著相关。各医院TT组LPOH发生率为0% ~ 5.88% (p = 0.0068);而在TE组和UPPP组中,发生率从0%到33.33%不等(p = 0.0413和p = 0.0409)。重复出血的发生不受治疗选择(再入院与门诊护理、观察与手术翻修、全身麻醉与局部麻醉)的影响。三组患者的出血严重程度不受年龄和性别的影响。在UPPP组中,抗凝剂的使用对LPOH严重程度有负面影响(p = 0.0166)。我们的样本中没有发生死亡;然而,术后出现3例严重出血(D级)。结论:术后晚期出血仍然是扁桃体相关手术的严重并发症,可能危及生命。手术技术和科室之间出血发生率的显著差异突出了标准化围手术期协议的必要性。虽然没有死亡病例发生,但严重病例的发生强调了警惕的术后监测的重要性。在我们的OSA队列中,扁桃体切除术显示出良好的安全性,最近的证据表明它可能是复发性扁桃体炎的一种有价值的替代方法,值得进一步研究。
{"title":"Epidemiology of late postoperative bleeding in OSA-related tonsil surgery: a multicentric retrospective study.","authors":"Jan Vodicka, Martin Chovanec, Milan Urik, Bretislav Gal, Rami Katra, Petr Skopek, Veronika Glumbikova, Anna Svejdova, Zdenek Knizek, Jan Kolin, Hana Dolezalova, Libor Sychra, Patrik Bursa, Lenka Jetmarova, Silvia Berkova, Pavel Strejcek, Josef Hajek, Tomas Kostlivy, David Slouka","doi":"10.32725/jab.2025.016","DOIUrl":"10.32725/jab.2025.016","url":null,"abstract":"<p><strong>Introduction: </strong>Tonsil-related procedures are considered fundamental and effective in the surgical treatment of obstructive sleep apnea (OSA). The range of techniques includes intratonsillar approaches, such as tonsillotomy (TT), as well as extracapsular procedures, such as tonsillectomy (TE) and uvulopalatopharyngoplasty (UPPP). Patients undergoing these procedures span all age groups, from children to seniors.</p><p><strong>Methods: </strong>This multicentric retrospective study, conducted between 2014 and 2018, analysed data from 3,498 patients who underwent bilateral TT, TE, or UPPP for OSA or ronchopathy. The cohort included 2,221 men (63.49%) and 1,277 women (36.51%). Of these, 2,808 patients (80.27%) underwent TT, 226 (6.46%) underwent TE, and 464 (13.26%) underwent UPPP.</p><p><strong>Results: </strong>Late postoperative haemorrhage (LPOH) occurrence was significantly associated with the type of surgery (p < 0.0001) and the hospital where the procedure was performed (p < 0.0001). The incidence of LPOH in the TT group ranged from 0% to 5.88% across hospitals (p = 0.0068); whereas in the TE and UPPP groups, rates ranged from 0% to 33.33% (p = 0.0413 and p = 0.0409, respectively). The occurrence of repetitive bleeding was not influenced by treatment choice (readmission vs. outpatient care, observation vs. surgical revision, general vs. local anaesthesia). The severity of bleeding in all three groups was not affected by age and gender. The use of anticoagulants negatively impacted LPOH severity (p = 0.0166) in the UPPP group. No deaths occurred in our sample; however, three cases of severe postoperative bleeding (grade \"D\") were observed.</p><p><strong>Conclusion: </strong>Late postoperative haemorrhage remains a serious complication of tonsil-related surgery with the potential for life-threatening outcomes. The marked variability in bleeding incidence between surgical techniques and departments highlights the need for standardised perioperative protocols. Although no fatalities occurred, the occurrence of severe cases underlines the importance of vigilant postoperative monitoring. In our OSA cohort, tonsillotomy showed favourable safety, and recent evidence suggests it may represent a valuable alternative also in recurrent tonsillitis, warranting further research.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 3","pages":"126-137"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199518","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
Serum xanthine oxidoreductase and oxidative stress are associated with bladder cancer: a case-control study from Jordan. 血清黄嘌呤氧化还原酶和氧化应激与膀胱癌有关:约旦的一项病例对照研究。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-01 Epub Date: 2025-09-25 DOI: 10.32725/jab.2025.015
Lina Elsalem, Abrar A Aleikish, Nosayba Al-Azzam, Mahmoud A Alfaqih, Haneen A Basheer, Omar Halalsheh

Xanthine oxidoreductase (XOR) is an oxidant enzyme that exists mainly in two distinct forms: the dehydrogenase form [xanthine dehydrogenase (XDH)] and the oxidized form [xanthine oxidase (XO)]. XO might contribute to tumorigenesis through direct metabolic activation of carcinogens and indirect generation of free radicals. Oxidative stress is one of the leading causes of bladder cancer (BC). Smoking and genetic susceptibility are also linked to oxidative stress and BC. This study investigated the association between XO serum levels and XOR genetic polymorphisms with BC. A case-control study was conducted among 109 BC patients and 109 controls matched by age, gender, body mass index, and smoking status. Serum levels of XO and 8-hydroxy-2'-deoxyguanosine (8-OhdG) were measured using ELISA, while thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC) were assessed using colorimetric assays. XOR single nucleotide polymorphisms were analyzed via tetra-primer ARMS-PCR. XO levels were significantly higher in BC patients than in controls [(5.11 ± 0.28 vs 3.83 ± 0.23) ng/ml, respectively (p < 0.0006)]. Among smokers, XO levels were also elevated in BC cases compared with controls [(5.29 ± 0.35 vs 3.41 ± 0.28) ng/ml, respectively (p < 0.0001)]. Oxidative stress biomarkers were elevated in BC patients compared with controls: 8-OHdG (19.39 ± 1.37 vs 16.32 ± 1.37 nmol/l), PC (8.88 ± 0.56 vs 4.42 ± 0.56) nmol/mg of protein, and TBARS (4.23 vs 3.15) µmol/ml, respectively (p < 0.05). Haplotype analysis showed that TGTCA, TGTA, TGA, and GTA were more frequent in BC patients and associated with increased BC status [4.17 (1.16-15.00), 1.84 (1.11-3.05), 1.62 (1.01-2.60), and 1.66 (1.02-2.71) fold increase in risk, respectively (p < 0.05)]. Elevated XO and oxidative stress markers are associated with BC, supporting their role in BC pathogenesis. Our findings suggest that they may act as potential diagnostic or therapeutic targets. However, mechanistic studies are required to clarify whether XO/oxidative stress markers contribute directly to carcinogenesis or reflects general redox imbalance in malignancy. Specific XOR haplotypes might serve as biomarkers for BC.

黄嘌呤氧化还原酶(XOR)是一种氧化酶,主要以两种不同的形式存在:脱氢酶形式[黄嘌呤脱氢酶(XDH)]和氧化形式[黄嘌呤氧化酶(XO)]。XO可能通过致癌物质的直接代谢激活和自由基的间接产生参与肿瘤的发生。氧化应激是膀胱癌(BC)的主要原因之一。吸烟和遗传易感性也与氧化应激和BC有关。本研究探讨了血清XO水平和与BC相关的XOR基因多态性之间的关系。在109名BC患者和109名对照者中进行了一项病例对照研究,对照者的年龄、性别、体重指数和吸烟状况相匹配。ELISA法测定血清XO和8-羟基-2′-脱氧鸟苷(8-OhdG)水平,比色法测定硫代巴比妥酸反应物质(TBARS)和蛋白羰基(PC)水平。通过四引物ARMS-PCR分析XOR单核苷酸多态性。BC患者的XO水平显著高于对照组[分别为(5.11±0.28 vs 3.83±0.23)ng/ml, p < 0.0006]。在吸烟者中,与对照组相比,BC患者的XO水平也升高[分别为(5.29±0.35 vs 3.41±0.28)ng/ml, p < 0.0001]。与对照组相比,BC患者的氧化应激生物标志物升高:8-OHdG(19.39±1.37 vs 16.32±1.37 nmol/l), PC(8.88±0.56 vs 4.42±0.56)nmol/mg蛋白质,TBARS (4.23 vs 3.15)µmol/ml (p < 0.05)。单倍型分析显示,TGTCA、TGTA、TGA和GTA在BC患者中更为常见,且与BC状态升高相关[风险分别增加4.17(1.16-15.00)、1.84(1.11-3.05)、1.62(1.01-2.60)、1.66(1.02-2.71)倍(p < 0.05)]。升高的XO和氧化应激标志物与BC有关,支持它们在BC发病机制中的作用。我们的研究结果表明,它们可能作为潜在的诊断或治疗靶点。然而,需要进行机制研究来阐明XO/氧化应激标志物是否直接参与致癌,还是反映了恶性肿瘤中普遍的氧化还原失衡。特异的XOR单倍型可能作为BC的生物标志物。
{"title":"Serum xanthine oxidoreductase and oxidative stress are associated with bladder cancer: a case-control study from Jordan.","authors":"Lina Elsalem, Abrar A Aleikish, Nosayba Al-Azzam, Mahmoud A Alfaqih, Haneen A Basheer, Omar Halalsheh","doi":"10.32725/jab.2025.015","DOIUrl":"https://doi.org/10.32725/jab.2025.015","url":null,"abstract":"<p><p>Xanthine oxidoreductase (XOR) is an oxidant enzyme that exists mainly in two distinct forms: the dehydrogenase form [xanthine dehydrogenase (XDH)] and the oxidized form [xanthine oxidase (XO)]. XO might contribute to tumorigenesis through direct metabolic activation of carcinogens and indirect generation of free radicals. Oxidative stress is one of the leading causes of bladder cancer (BC). Smoking and genetic susceptibility are also linked to oxidative stress and BC. This study investigated the association between XO serum levels and XOR genetic polymorphisms with BC. A case-control study was conducted among 109 BC patients and 109 controls matched by age, gender, body mass index, and smoking status. Serum levels of XO and 8-hydroxy-2'-deoxyguanosine (8-OhdG) were measured using ELISA, while thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC) were assessed using colorimetric assays. XOR single nucleotide polymorphisms were analyzed via tetra-primer ARMS-PCR. XO levels were significantly higher in BC patients than in controls [(5.11 ± 0.28 vs 3.83 ± 0.23) ng/ml, respectively (p < 0.0006)]. Among smokers, XO levels were also elevated in BC cases compared with controls [(5.29 ± 0.35 vs 3.41 ± 0.28) ng/ml, respectively (p < 0.0001)]. Oxidative stress biomarkers were elevated in BC patients compared with controls: 8-OHdG (19.39 ± 1.37 vs 16.32 ± 1.37 nmol/l), PC (8.88 ± 0.56 vs 4.42 ± 0.56) nmol/mg of protein, and TBARS (4.23 vs 3.15) µmol/ml, respectively (p < 0.05). Haplotype analysis showed that TGTCA, TGTA, TGA, and GTA were more frequent in BC patients and associated with increased BC status [4.17 (1.16-15.00), 1.84 (1.11-3.05), 1.62 (1.01-2.60), and 1.66 (1.02-2.71) fold increase in risk, respectively (p < 0.05)]. Elevated XO and oxidative stress markers are associated with BC, supporting their role in BC pathogenesis. Our findings suggest that they may act as potential diagnostic or therapeutic targets. However, mechanistic studies are required to clarify whether XO/oxidative stress markers contribute directly to carcinogenesis or reflects general redox imbalance in malignancy. Specific XOR haplotypes might serve as biomarkers for BC.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 3","pages":"107-116"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199472","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
Influence of the antidiabetic drug metformin on the aquatic crustacean Daphnia magna. 降糖药二甲双胍对水生甲壳动物大水蚤的影响。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-01 Epub Date: 2025-08-21 DOI: 10.32725/jab.2025.011
Martina Poncarova, Sarka Klementova, Michal Sorf

Background: The antidiabetic drug metformin has been repeatedly detected in surface waters worldwide. This study investigates the effects of the environmentally relevant concentration of metformin on a non-target aquatic organism - a freshwater crustacean, Daphnia magna, with an emphasis on the stress response of daphnids and the long-term effects on their consecutive generations.

Methods: The chronic toxicity test and the consecutive generations test were inspired by the OECD method. The total antioxidant capacity (Trolox equivalent - TEAC), superoxide dismutase (SOD) activity, and catalase (CAT) activity were related to the protein content in the tested daphnids.

Results: Elevated antioxidant activities were revealed in daphnids exposed to metformin in comparison to the control group (1.9 × for TEAC, 1.7 × for SOD; 1.3 × for CAT). Furthermore, diminished body sizes and malformations in the digestive system, spine and carapace were detected in newborn juveniles in the second and third generations exposed to metformin.

Conclusion: Long-term exposure to metformin in environmentally relevant concentrations led to a significant detrimental reaction in aquatic crustaceans.

背景:降糖药二甲双胍在世界各地地表水中多次检出。本研究研究了环境相关浓度二甲双胍对非靶水生生物淡水甲壳类大水蚤的影响,重点研究了水蚤的应激反应及其对其后代的长期影响。方法:采用OECD法进行慢性毒性试验和连续代试验。水蚤总抗氧化能力(Trolox equivalent - TEAC)、超氧化物歧化酶(SOD)活性和过氧化氢酶(CAT)活性与蛋白质含量有关。结果:与对照组相比,暴露于二甲双胍的水蚤抗氧化活性升高(TEAC 1.9倍,SOD 1.7倍,CAT 1.3倍)。此外,在暴露于二甲双胍的第二代和第三代新生幼鱼中发现了体型缩小和消化系统、脊柱和甲壳的畸形。结论:长期暴露于环境相关浓度的二甲双胍会导致水生甲壳类动物发生显著的有害反应。
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引用次数: 0
Secondary metabolites from halotolerant filamentous fungi as potential topical cosmeceutical ingredients. 耐盐丝状真菌的次生代谢物作为潜在的局部药妆成分。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-01 Epub Date: 2025-09-23 DOI: 10.32725/jab.2025.013
Chi Hoang, Ha Tran, Hang Tran, Diep Hoang, Quan Nguyen, Cuong Le

The use of natural products in cosmetics and pharmacy has risen dramatically in recent years, leading to the overexploitation of flora and fauna worldwide and threatening the environmental sustainability. Microbe-derived components could help to solve the problem due to their independently controllable cultural property. To investigate the potential of microfungi for producing potential novel cosmeceuticals, cerevisterol (1), aloesol (2), 3β,5α,9α-trihydroxyergosta-7,22-diene-6-one (3), and ergosterol peroxide (4) were isolated from the halotolerant fungal strains Penicillium brefeldianum CL6 and Talaromyces sp. S3-Rt-N3. They were then tested for biological properties, including anti-microbial, tyrosinase inhibitory, and wound healing activities. The results revealed the wound-healing potentials of two fungal compounds - (1) and (2) - in terms of cell proliferation promotion in NIH-3T3 murine fibroblasts, and the tyrosinase inhibitory potential of fungal compounds (1), (3), and (4) in the substrates L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA). Interestingly, compound (1) exhibited antimicrobial activity against acne-causing bacterium Propionibacterium acnes. These results have revealed new prospects for the application of microorganisms-derived compounds, especially in the cosmetics industry.

近年来,天然产品在化妆品和制药领域的使用急剧增加,导致世界范围内动植物的过度开发,并威胁到环境的可持续性。微生物衍生成分可以帮助解决这一问题,因为它们具有独立可控的文化特性。为了研究微真菌生产潜在新型药药的潜力,从耐盐真菌青霉brefeldium CL6和Talaromyces sp. S3-Rt-N3中分离出麦角甾醇(1)、芦荟醇(2)、3β、5α、9α-三羟基麦角甾醇-7,22-二烯-6-one(3)和麦角甾醇过氧化物(4)。然后测试它们的生物学特性,包括抗微生物、酪氨酸酶抑制和伤口愈合活性。结果揭示了真菌化合物(1)和(2)在促进NIH-3T3小鼠成纤维细胞增殖方面的伤口愈合潜力,真菌化合物(1)、(3)和(4)对底物l -酪氨酸和l -3,4-二羟基苯丙氨酸(L-DOPA)的酪氨酸酶抑制潜力。有趣的是,化合物(1)对引起痤疮的细菌痤疮丙酸杆菌具有抗菌活性。这些结果揭示了微生物衍生化合物的新应用前景,特别是在化妆品行业。
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引用次数: 0
Characteristics of healthy sinonasal microbiome - single-centre study in the Czech Republic. 健康鼻腔微生物群的特征——捷克共和国的单中心研究。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-01 Epub Date: 2025-09-26 DOI: 10.32725/jab.2025.012
Kristyna Maminak, Karla Janouskova, Richard Holy, Alzbeta Prasilova, Tomas Filipovsky, Daniel Kovar, Jaromir Astl

Introduction: The human nasal cavity and paranasal sinuses host a complex and dynamic microbiome which has a crucial role in mucosal immunity. A comprehensive profile of the healthy sinonasal microbiome remains limited. The purpose of our study was to characterize the healthy sinonasal microbiome in adults using 16S rRNA long-read sequencing to enable species-level resolution, and to assess its associations with demographical and clinical factors such as smoking, allergy history, and olfactory function.

Study design: We performed a prospective, single-centre study analysing middle meatus samples from 27 healthy individuals undergoing septoplasty in the age range from 21 to 57 years, excluding those with antibiotic and corticosteroid use and those with signs of acute or chronic rhinosinusitis.

Results: A high interindividual variability in the composition of healthy sinonasal microbiome was observed. At the phylum level, it was dominated by Firmicutes (48.96%), Actinobacteria (34.83%), and Proteobacteria (13.85%), while Firmicutes and Actinobacteria were consistently present in all samples. At the genus level, Staphylococcus spp. (32.32%), Cutibacterium (28.04%), and Corynebacterium (4.66%) were most abundant. We observed trend level correlations between phyla and some clinical factors (e.g., smoking and olfactory dysfunction) and selected phyla. However, none remained significant after false discovery rate (FDR) correction across taxa.

Conclusion: The study proposes Staphylococcus spp., Corynebacterium spp., and Cutibacterium spp. to be a core taxa in the healthy sinonasal microbiome. Amid the interindividual diversity in our cohort, there was evidence of a stable core microbiome potentially influenced by environmental and host factors. Our findings suggest a baseline reference for distinguishing a dysbiosis in upper respiratory disease.

人类的鼻腔和鼻窦是一个复杂而动态的微生物群的宿主,在粘膜免疫中起着至关重要的作用。对健康鼻窦微生物群的全面研究仍然有限。本研究的目的是利用16S rRNA长读测序技术来表征健康成人鼻腔微生物组,以实现物种水平的分辨率,并评估其与人口统计学和临床因素(如吸烟、过敏史和嗅觉功能)的关联。研究设计:我们进行了一项前瞻性单中心研究,分析了27名年龄在21至57岁之间接受鼻中隔成形术的健康个体的中间道样本,排除了使用抗生素和皮质类固醇以及有急性或慢性鼻窦炎症状的患者。结果:观察到健康鼻腔微生物组组成的高度个体间变异性。在门水平上,以厚壁菌门(48.96%)、放线菌门(34.83%)和变形菌门(13.85%)为主,而厚壁菌门和放线菌门在所有样品中一致存在。属水平上以葡萄球菌(Staphylococcus spp.)、Cutibacterium(28.04%)和棒状杆菌(棒状杆菌)最多(4.66%)。我们观察了门与一些临床因素(如吸烟和嗅觉功能障碍)之间的趋势水平相关性,并选择了门。然而,在整个分类群的错误发现率(FDR)校正后,没有一个仍然显着。结论:本研究认为葡萄球菌、棒状杆菌和表皮杆菌是健康鼻窦微生物群的核心类群。在我们的队列中的个体间多样性中,有证据表明稳定的核心微生物组可能受到环境和宿主因素的影响。我们的研究结果为区分上呼吸道疾病的生态失调提供了一个基线参考。
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引用次数: 0
Applying the technology ORBEYETM exoscope in transoral exoscopic laryngeal surgery: single centre prospective study. ORBEYETM外窥镜技术在喉经口外窥镜手术中的应用:单中心前瞻性研究。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-01 Epub Date: 2025-08-21 DOI: 10.32725/jab.2025.010
Richard Holy, Tomas Filipovsky, Eva Lukavcova, David Kalfert, Pavol Prazenica, Petra Dytrych, Jiri Hlozek, Jan Rotnagl, Daniel Kovar, Jaromir Astl

Introduction: ORBEYETM exoscope offers superior visualization with clearer imaging compared to standard methods and supports narrow band imaging (NBI). ORBEYETM provides better visualization of tissue structures, thus increasing the accuracy of the surgical procedure. The systematic use of ORBEYETM in transoral exoscopic laryngeal surgery (TOLES) is rarely documented. This study evaluates the sensitivity and specificity of TOLES using ORBEYETM with white light and NBI modalities.

Methods: Between 8/2021 and 8/2024, 84 patients underwent TOLES using ORBEYETM with white light and NBI modes. All surgeries were performed in a specialized setting with consistent preoperative and intraoperative imaging protocols.

Results: TOLES using ORBEYETM was successfully performed in all 84 patients. A statistically significant dependence (p < 0.001) was observed between preoperative/perioperative (TOLES) findings and definitive histology for both white light and NBI modalities. ORBEYETM facilitated detailed imaging of tissue structures and allowed targeted biopsies.

Conclusion: TOLES with perioperative NBI/white light endoscopy achieved a high correlation between pre-histopathological diagnoses and final histopathological results. ORBEYETM exoscope provides three-dimensional 4K resolution, superior imaging, and improved ergonomics for the surgeon, reducing workload and increasing efficiency. It delivered more efficient surgical team collaboration and experience sharing. The integration of NBI into the TOLES system facilitated accurate navigation and targeting of the biopsy, helping to establish correct definitive diagnosis. TOLES showed more accurate scoring of perioperative NBI findings.

与标准方法相比,ORBEYETM exoscope提供了更清晰的可视化成像,并支持窄带成像(NBI)。ORBEYETM提供了更好的组织结构可视化,从而提高了手术过程的准确性。ORBEYETM在经口外窥镜喉部手术(TOLES)中的系统应用很少有文献记载。本研究利用ORBEYETM与白光和NBI模式评估TOLES的敏感性和特异性。方法:在2021年8月至2024年8月期间,84例患者使用ORBEYETM白光和NBI模式进行TOLES手术。所有手术均在专门的环境下进行,术前和术中成像协议一致。结果:84例患者均成功应用ORBEYETM进行TOLES手术。术前/围手术期(TOLES)检查结果与白光和NBI模式的明确组织学之间存在统计学上显著的依赖性(p < 0.001)。ORBEYETM有助于组织结构的详细成像,并允许有针对性的活检。结论:围手术期NBI/白光内镜下的TOLES在组织病理学前诊断和最终组织病理学结果之间具有很高的相关性。ORBEYETM外窥镜为外科医生提供三维4K分辨率,卓越的成像和改进的人体工程学,减少工作量,提高效率。它提供了更有效的外科团队协作和经验分享。将NBI整合到TOLES系统中有助于准确导航和定位活检,有助于建立正确的明确诊断。TOLES对围手术期NBI的评分更为准确。
{"title":"Applying the technology ORBEYE<sup>TM</sup> exoscope in transoral exoscopic laryngeal surgery: single centre prospective study.","authors":"Richard Holy, Tomas Filipovsky, Eva Lukavcova, David Kalfert, Pavol Prazenica, Petra Dytrych, Jiri Hlozek, Jan Rotnagl, Daniel Kovar, Jaromir Astl","doi":"10.32725/jab.2025.010","DOIUrl":"https://doi.org/10.32725/jab.2025.010","url":null,"abstract":"<p><strong>Introduction: </strong>ORBEYE<sup>TM</sup> exoscope offers superior visualization with clearer imaging compared to standard methods and supports narrow band imaging (NBI). ORBEYE<sup>TM</sup> provides better visualization of tissue structures, thus increasing the accuracy of the surgical procedure. The systematic use of ORBEYE<sup>TM</sup> in transoral exoscopic laryngeal surgery (TOLES) is rarely documented. This study evaluates the sensitivity and specificity of TOLES using ORBEYE<sup>TM</sup> with white light and NBI modalities.</p><p><strong>Methods: </strong>Between 8/2021 and 8/2024, 84 patients underwent TOLES using ORBEYE<sup>TM</sup> with white light and NBI modes. All surgeries were performed in a specialized setting with consistent preoperative and intraoperative imaging protocols.</p><p><strong>Results: </strong>TOLES using ORBEYE<sup>TM</sup> was successfully performed in all 84 patients. A statistically significant dependence (p < 0.001) was observed between preoperative/perioperative (TOLES) findings and definitive histology for both white light and NBI modalities. ORBEYE<sup>TM</sup> facilitated detailed imaging of tissue structures and allowed targeted biopsies.</p><p><strong>Conclusion: </strong>TOLES with perioperative NBI/white light endoscopy achieved a high correlation between pre-histopathological diagnoses and final histopathological results. ORBEYE<sup>TM</sup> exoscope provides three-dimensional 4K resolution, superior imaging, and improved ergonomics for the surgeon, reducing workload and increasing efficiency. It delivered more efficient surgical team collaboration and experience sharing. The integration of NBI into the TOLES system facilitated accurate navigation and targeting of the biopsy, helping to establish correct definitive diagnosis. TOLES showed more accurate scoring of perioperative NBI findings.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 3","pages":"138-143"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199492","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
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