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.
{"title":"Propofol suppresses breast cancer invasion: An in vitro three-dimensional cell invasion model with microfluidic technology.","authors":"Zhitong Wan, Haoyue Lyu, Yuting Luo, Tong Liu, Xiaoyu Peng, Yijing Zhang, Yuan Li","doi":"10.32725/jab.2025.019","DOIUrl":"https://doi.org/10.32725/jab.2025.019","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 4","pages":"174-183"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768101","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}
Pub Date : 2025-12-01Epub Date: 2025-10-30DOI: 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.
{"title":"Relationship between interleukin-37 genetic polymorphisms and HBV-related liver disease in a Chinese Han cohort.","authors":"Ping Fang, Ping Meng, Lijun Du, Hui Li, Rong Wang, Juan Zhao, Decheng Cai","doi":"10.32725/jab.2025.017","DOIUrl":"10.32725/jab.2025.017","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 4","pages":"184-196"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768174","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}
Pub Date : 2025-12-01Epub Date: 2025-12-08DOI: 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.
{"title":"Exosomes from LPS-stimulated macrophages alleviate neuroinflammatory responses by reducing pyroptosis in systemic lipopolysaccharide-induced mice.","authors":"Tao Ying, Zhezhe Sun","doi":"10.32725/jab.2025.018","DOIUrl":"https://doi.org/10.32725/jab.2025.018","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 4","pages":"163-173"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768059","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}
Pub Date : 2025-09-01Epub Date: 2025-09-25DOI: 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。
{"title":"Elevated plasma levels of cell-free mtDNA are associated with acute rejection following heart transplantation.","authors":"Dana Dlouha, Kristyna Janouskova, Sarka Chytilova, Jevgenija Vymetalova, Marianna Lukasova, Sarka Novakova, Eva Rohlova, Jaroslav A Hubacek","doi":"10.32725/jab.2025.014","DOIUrl":"https://doi.org/10.32725/jab.2025.014","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 3","pages":"97-106"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199533","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}
Pub Date : 2025-09-01Epub Date: 2025-09-29DOI: 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.
{"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}
Pub Date : 2025-09-01Epub Date: 2025-09-25DOI: 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}
Pub Date : 2025-09-01Epub Date: 2025-08-21DOI: 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.
{"title":"Influence of the antidiabetic drug metformin on the aquatic crustacean Daphnia magna.","authors":"Martina Poncarova, Sarka Klementova, Michal Sorf","doi":"10.32725/jab.2025.011","DOIUrl":"https://doi.org/10.32725/jab.2025.011","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Long-term exposure to metformin in environmentally relevant concentrations led to a significant detrimental reaction in aquatic crustaceans.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 3","pages":"144-151"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199498","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}
Pub Date : 2025-09-01Epub Date: 2025-09-23DOI: 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.
{"title":"Secondary metabolites from halotolerant filamentous fungi as potential topical cosmeceutical ingredients.","authors":"Chi Hoang, Ha Tran, Hang Tran, Diep Hoang, Quan Nguyen, Cuong Le","doi":"10.32725/jab.2025.013","DOIUrl":"https://doi.org/10.32725/jab.2025.013","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 3","pages":"152-162"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199549","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}
Pub Date : 2025-09-01Epub Date: 2025-09-26DOI: 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.
{"title":"Characteristics of healthy sinonasal microbiome - single-centre study in the Czech Republic.","authors":"Kristyna Maminak, Karla Janouskova, Richard Holy, Alzbeta Prasilova, Tomas Filipovsky, Daniel Kovar, Jaromir Astl","doi":"10.32725/jab.2025.012","DOIUrl":"https://doi.org/10.32725/jab.2025.012","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Study design: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14912,"journal":{"name":"Journal of applied biomedicine","volume":"23 3","pages":"117-125"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199479","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}
Pub Date : 2025-09-01Epub Date: 2025-08-21DOI: 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.
{"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}