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CXCL12/CXCR4 as a potential axis in diagnosis and predicting disease severity in COVID-19 patients: a new perspective CXCL12/CXCR4作为诊断和预测COVID-19患者疾病严重程度的潜在轴心:一个新视角
Pub Date : 2024-07-22 DOI: 10.1515/tjb-2023-0193
Alev Lazoğlu Ozkaya, Esra Laloğlu, Albulhakim Hasan Gul, N. Çelik
Coronavirus disease 2019 (COVID-19) exhibits variations in terms of patients’ clinical symptoms and levels of routinely employed biochemical markers. The aim of the current study was to determine the correlation between serum levels of the C-X-C chemokine ligand type 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4), one of its specific receptors, and disease severity in COVID-19 patients. Sixty-nine patients were diagnosed with COVID-19 from February to July 2021, and a healthy control group of 39 individuals were enrolled in the study. Patients were divided into subgroups: mild-moderate and severe. Serum CXCL12 and CXCR4 levels were measured using the enzyme-linked immunosorbent assay method. CXCL12 and CXCR4 concentrations were both significantly higher in the clinically severe disease group compared to the mild-moderate disease group (p<0.05 in both groups). CXCL12 and CXCR4 levels were also significantly higher in the patients with clinically mild-moderate disease compared to the control group (p<0.001 and p<0.05, respectively). Both CXCL12 and CXCR4 levels were correlated with clinical severity. Serum CXCL12 and CXCR4 levels were significantly positively correlated. Assuming a cut-off value of 1.44 ng/mL, serum CXCL12 levels showed 98 % sensitivity and 84 % specificity to distinguish between COVID-19 patients and healthy individuals (AUC=0.98, p<0.001, 95 % CI=0.95–1.0). Serum CXCR4 levels distinguished individuals with COVID-19 from healthy controls with 88 % sensitivity and 72 % specificity at a cut-off value of 69.7 pg/mL (AUC=0.82, p<0.001, 95 % CI=0.74–0.9). Serum CXCL12 and CXCR4 levels may be included among the biomarkers used to differentiate patients with COVID-19 and determine the clinical severity of the disease.
2019年冠状病毒病(COVID-19)在患者临床症状和常规生化指标水平方面表现出差异。本研究旨在确定COVID-19患者血清中C-X-C趋化因子配体12型(CXCL12)及其特异受体之一C-X-C趋化因子受体4型(CXCR4)的水平与疾病严重程度之间的相关性。 研究共纳入了 2021 年 2 月至 7 月期间确诊的 69 名 COVID-19 患者和 39 名健康对照组。患者被分为轻度-中度和重度两个亚组。采用酶联免疫吸附法测定血清 CXCL12 和 CXCR4 水平。 与轻中度疾病组相比,临床重度疾病组的 CXCL12 和 CXCR4 浓度均明显升高(两组的 P 均<0.05)。临床轻中度疾病患者的 CXCL12 和 CXCR4 水平也明显高于对照组(分别为 p<0.001 和 p<0.05)。CXCL12和CXCR4水平均与临床严重程度相关。血清 CXCL12 和 CXCR4 水平呈显著正相关。假设截断值为 1.44 纳克/毫升,血清 CXCL12 水平在区分 COVID-19 患者和健康人方面显示出 98% 的灵敏度和 84% 的特异性(AUC=0.98,p<0.001,95% CI=0.95-1.0)。以69.7 pg/mL为临界值,血清CXCR4水平区分COVID-19患者和健康对照者的灵敏度为88%,特异度为72%(AUC=0.82,p<0.001,95 % CI=0.74-0.9)。 血清 CXCL12 和 CXCR4 水平可作为生物标志物,用于区分 COVID-19 患者并确定疾病的临床严重程度。
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引用次数: 0
Human estrogen receptor alpha (ERα) targeted cyclic peptides inhibit cell growth and induce apoptosis in MCF-7 cells 人雌激素受体α(ERα)靶向环肽抑制 MCF-7 细胞生长并诱导其凋亡
Pub Date : 2024-07-18 DOI: 10.1515/tjb-2024-0123
Hilal Şentürk, Huri Dedeakayoğulları, İlke U. Marion, S. Özçubukçu, M. S. Kesici, Şeyma Ünsal Beyge, Muradiye Acar, Merve Erkısa Genel, F. Akbaş, E. Ulukaya
Human estrogen receptor alpha (ERα) is considered an important target, especially in the treatment of breast cancer, as it has a vital role in cancer development. ERα-targeted therapies generally target the ligand binding domain (LBD) of ERα. However, over time, cells develop resistance to this mechanism alternative approaches to inhibit ERα activity target ERα–DNA or ERα–cofactor interactions. Inhibitors of ERα–cofactor interactions are designed by targeting the hydrophobic hollow region of the receptor box LXXLL motif. In this context, helix-stabilized cyclic peptides (SPs) designed with in silico approaches were obtained by solid phase peptide synthesis. The effects of SPs on MCF-7 cells were examined with MTT and ATP, and qPCR and flow cytometry were used for further analysis. Our results demonstrated that the SPs were effective only in MCF-7 cells expressing ERα. In addition, cyclic peptide combinations (SPCs) showed anti-proliferative and toxic effects on MCF-7 cells. The impact of SPCs with the highest inhibitory effect in MCF-7 cells on ERα-related genes and markers of apoptosis was revealed. Moreover, the flow cytometry analysis result used to examine apoptotic cells proved the apoptosis of SPCs in MCF-7 cells. These findings suggest that our novel SPs, which inhibit coactivator interactions of ERα, induce apoptosis of MCF-7 cells. Thus, considering this strong effect of SPs in the inhibition of receptors, it is pointed out that they can be further developed as an alternative to current clinical treatments or as an auxiliary approach in the generating of new targeted peptide-based therapies.
人类雌激素受体α(ERα)被认为是一个重要的靶点,尤其是在治疗乳腺癌方面,因为它在癌症的发展中起着至关重要的作用。ERα靶向疗法通常以ERα的配体结合域(LBD)为靶点。然而,随着时间的推移,细胞会对这一机制产生抗药性,而抑制ERα活性的替代方法则以ERα-DNA或ERα-cofactor相互作用为目标。ERα-因子相互作用的抑制剂是通过靶向受体盒 LXXLL 动机的疏水中空区域而设计的。 在此背景下,通过固相肽合成获得了用硅学方法设计的螺旋稳定环肽(SPs)。用 MTT 和 ATP 检测了 SPs 对 MCF-7 细胞的影响,并使用 qPCR 和流式细胞仪进行了进一步分析。 结果表明,SPs 只对表达 ERα 的 MCF-7 细胞有效。此外,环肽组合(SPCs)对 MCF-7 细胞具有抗增殖和毒性作用。对 MCF-7 细胞抑制作用最强的 SPCs 对 ERα 相关基因和细胞凋亡标志物的影响也得到了揭示。此外,用于检测凋亡细胞的流式细胞术分析结果也证明了 SPCs 对 MCF-7 细胞的凋亡作用。 这些发现表明,我们的新型 SPs 可抑制 ERα 辅激活剂的相互作用,诱导 MCF-7 细胞凋亡。因此,考虑到 SPs 在抑制受体方面的强大作用,我们指出,可以进一步开发 SPs,将其作为当前临床疗法的替代品,或作为产生基于肽的新型靶向疗法的辅助方法。
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引用次数: 0
In vitro and in silico investigations of the pro-apoptotic activity of Opuntia ficus-indica cladode extracts against K562 cells 欧蓬荚果提取物对 K562 细胞促凋亡活性的体外和硅学研究
Pub Date : 2024-07-15 DOI: 10.1515/tjb-2023-0229
Şule Öncül, E. Becer, Pınar Mega Tiber, K. Teralı, A. Aykaç
Cladodes of Opuntia ficus-indica (OFI) are thought to be an excellent source of bioactive compounds, making them an aspirant for the manufacture of health-promoting compounds. This study aims at exploring the pro-apoptotic effects of spiny and thornless OFI cladode extracts on the human immortalized myelogenous leukemia cell line (K562). The ethanol extraction method was used for preparing cladode extract. Cytotoxicity was evaluated by MTT assays. Membrane permeability/damage was detected by annexin V-binding assays, and mitochondrial damage/alteration was detected by mitochondrial membrane potential measurements. The protein expression quantities of Bax and Bcl-2 were assessed by Western blotting. The pro-apoptotic potentials of the main spiny and thornless OFI extract constituents were investigated structurally and mechanistically using protein–ligand docking and interaction profiling. Spiny OFI extract displayed a stronger cytotoxic effect than thornless OFI extract on K562 cells. In silico findings agreed with the pro-apoptotic action observed in vitro. Finally, our findings imply that OFI extracts cause apoptosis in K562 cells in order to have anti-cancer effects.
据认为,Opuntia ficus-indica(OFI)的苞片是生物活性化合物的极佳来源,使其成为生产促进健康的化合物的理想原料。本研究旨在探究有刺和无刺蝙蝠蛾科植物苞片提取物对人类永生化骨髓性白血病细胞系(K562)的促凋亡作用。 采用乙醇萃取法制备药材提取物。细胞毒性通过 MTT 试验进行评估。膜通透性/损伤通过附件素 V 结合试验进行检测,线粒体损伤/改变通过线粒体膜电位测量进行检测。Bax 和 Bcl-2 的蛋白表达量通过 Western 印迹法进行评估。通过蛋白质配体对接和相互作用分析,从结构和机理上研究了有刺和无刺 OFI 提取物主要成分的促凋亡潜能。 与无刺 OFI 提取物相比,有刺 OFI 提取物对 K562 细胞具有更强的细胞毒性作用。硅学研究结果与体外观察到的促凋亡作用一致。 最后,我们的研究结果表明,OFI 提取物会导致 K562 细胞凋亡,从而产生抗癌作用。
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引用次数: 0
Evaluation of the implementation of the rational use of laboratory tests in the clinical chemistry laboratory 评估临床化学实验室合理使用化验项目的实施情况
Pub Date : 2024-07-02 DOI: 10.1515/tjb-2023-0132
H. Serin, Bağnu Orhan, Merve S. Say, H. Arslan, Sinemis Inal, B. B. Inal, Mehmet Şeneş
Abstract Objectives The ‘Rational Laboratory Use Project’ (RLUP) was launched in 2018 by the Department of Examination and Diagnosis Services under the General Directorate of Health Services of the Republic of Turkey’s Ministry of Health. In this study, we aimed to determine the rate of implementation of RLUP in medical biochemistry laboratories, and to contribute to new regulations by collecting the information and opinions of the laboratory experts participating the survey. Methods Thirty questions were uploaded to an online survey tool (SurveyMonkey®, San Mateo, ABD). The first five were descriptive for laboratories. Among the remaining 25 questions, one is open-ended and addresses the various topics encompassed by the project’s scope. Results The questionnaire was completed by 202 medical biochemistry specialists, of whom 82.12 % reported that they did not implement autoverification. 55.65 % defined consultations in Hospital Management Information System (HIMS), but; 70.49 % were not using it actively. 57.69 % of the participants answered, “I agree” to the statement “I think RLUP is feasible”. It was observed that the specialists tried to implement rational laboratory practices partially depending on their laboratory capacity, hospital administration and Laboratory Information Management System (LIMS). Conclusions Increasing clinicians’ awareness could increase the success of this project, which might provide more effective diagnosis and treatment for the patient. In our view, actively involving stakeholders of the information management system, which is not under the direct control of laboratory professionals, in the RLUP will accelerate the development of the project.
摘要 目的 土耳其共和国卫生部卫生服务总局下属的检查和诊断服务部于2018年启动了 "实验室合理使用项目"(RLUP)。在本研究中,我们旨在通过收集参与调查的实验室专家的信息和意见,确定 RLUP 在医学生化实验室的实施率,并为新法规的制定做出贡献。方法 将 30 个问题上传到在线调查工具(SurveyMonkey®, San Mateo, ABD)。前五个问题是针对实验室的描述性问题。在其余 25 个问题中,有一个问题是开放式的,涉及项目范围内的各种主题。结果 202 名医学生物化学专家填写了调查问卷,其中 82.12 % 的专家表示他们没有实施自动核查。55.65%的人在医院管理信息系统(HIMS)中定义了会诊,但70.49%的人并未积极使用该系统。对于 "我认为 RLUP 是可行的 "这一说法,57.69% 的参与者回答 "我同意"。据观察,专家们尝试实施合理的实验室操作,部分取决于其实验室能力、医院管理和实验室信息管理系统(LIMS)。结论 提高临床医生的认识可增加该项目的成功率,从而为患者提供更有效的诊断和治疗。我们认为,让实验室专业人员无法直接控制的信息管理系统的利益相关者积极参与 RLUP,将加快项目的发展。
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引用次数: 0
Right vagotomy alters heart rate variability temporarily and increases total choline levels in rats 右迷走神经切断术可暂时改变大鼠的心率变异性并增加总胆碱水平
Pub Date : 2024-07-01 DOI: 10.1515/tjb-2024-0046
H. Kazdagli, E. Baris, Hasan Fehmi Ozel, Mustafa Ozbek
Abstract Objectives The variability in the time intervals between heartbeats, known as heart rate variability (HRV), serves as a reflection of the intricate interplay between the sympathetic and parasympathetic neural systems. While the potential asymmetric effects of the left and right branches of the vagus nerve remain uncertain, this study aims to investigate the impact of unilateral, bilateral, and atropine interventions on HRV parameters and choline levels within cardiac tissue. Methods 40 male adult Wistar albino rats were randomly assigned to the five groups (each n=8): sham-operated, atropine, right vagotomy, left vagotomy, and bilateral vagotomy. Heart rate variability (HRV) analyses were conducted, and the levels of total choline/acetylcholine in heart tissues were quantified. Statistical analyses were performed to assess the results. Results The bilateral vagotomy and atropine groups exhibited higher heart rates and high frequency power (HF), along with reduced low frequency power (LF). Total power (TP) remained relatively unchanged. In the bilateral vagotomy group, DFAα1 was significantly elevated while DFAα2 was reduced significantly. SD1 and SampEn were significantly lower in both the bilateral vagotomy and atropine groups. Notably, the right vagotomy group displayed significant changes primarily in the 15th minute, particularly in time-domain parameters, HF, TP, and SD1, with a significant increase observed in total choline levels. Conclusions Our results revealed that asymmetrical vagal innervation induces distinct effects on heart rate variability parameters and total choline/acetylcholine levels in heart tissues. Our findings suggest that compensatory hemodynamic recovery, possibly driven by contralateral vagal overactivity, may contribute to these observed results.
摘要 目的 心跳时间间隔的变化被称为心率变异性(HRV),它反映了交感神经系统和副交感神经系统之间错综复杂的相互作用。迷走神经左右分支的潜在非对称效应仍不确定,本研究旨在调查单侧、双侧和阿托品干预对心率变异参数和心脏组织内胆碱水平的影响。方法 将 40 只雄性成年 Wistar 白化大鼠随机分为五组(每组 8 只):假手术组、阿托品组、右迷走神经切断组、左迷走神经切断组和双侧迷走神经切断组。进行心率变异性(HRV)分析,并量化心脏组织中的总胆碱/乙酰胆碱水平。对结果进行了统计分析。结果 双侧迷走神经切断术组和阿托品组的心率和高频功率(HF)较高,而低频功率(LF)较低。总功率(TP)相对保持不变。在双侧迷走神经切断术组中,DFAα1 明显升高,而 DFAα2 则明显降低。双侧迷走神经切断术组和阿托品组的 SD1 和 SampEn 均明显降低。值得注意的是,右侧迷走神经切断术组主要在第 15 分钟出现明显变化,尤其是时域参数、HF、TP 和 SD1,同时观察到总胆碱水平明显增加。结论 我们的研究结果表明,不对称迷走神经支配会对心率变异性参数和心脏组织中的总胆碱/乙酰胆碱水平产生不同的影响。我们的研究结果表明,可能是对侧迷走神经过度活动导致的代偿性血流动力学恢复可能促成了这些观察到的结果。
{"title":"Right vagotomy alters heart rate variability temporarily and increases total choline levels in rats","authors":"H. Kazdagli, E. Baris, Hasan Fehmi Ozel, Mustafa Ozbek","doi":"10.1515/tjb-2024-0046","DOIUrl":"https://doi.org/10.1515/tjb-2024-0046","url":null,"abstract":"Abstract Objectives The variability in the time intervals between heartbeats, known as heart rate variability (HRV), serves as a reflection of the intricate interplay between the sympathetic and parasympathetic neural systems. While the potential asymmetric effects of the left and right branches of the vagus nerve remain uncertain, this study aims to investigate the impact of unilateral, bilateral, and atropine interventions on HRV parameters and choline levels within cardiac tissue. Methods 40 male adult Wistar albino rats were randomly assigned to the five groups (each n=8): sham-operated, atropine, right vagotomy, left vagotomy, and bilateral vagotomy. Heart rate variability (HRV) analyses were conducted, and the levels of total choline/acetylcholine in heart tissues were quantified. Statistical analyses were performed to assess the results. Results The bilateral vagotomy and atropine groups exhibited higher heart rates and high frequency power (HF), along with reduced low frequency power (LF). Total power (TP) remained relatively unchanged. In the bilateral vagotomy group, DFAα1 was significantly elevated while DFAα2 was reduced significantly. SD1 and SampEn were significantly lower in both the bilateral vagotomy and atropine groups. Notably, the right vagotomy group displayed significant changes primarily in the 15th minute, particularly in time-domain parameters, HF, TP, and SD1, with a significant increase observed in total choline levels. Conclusions Our results revealed that asymmetrical vagal innervation induces distinct effects on heart rate variability parameters and total choline/acetylcholine levels in heart tissues. Our findings suggest that compensatory hemodynamic recovery, possibly driven by contralateral vagal overactivity, may contribute to these observed results.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"11 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141700498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A brief history of hematology analyzers and recent advancements: the available testing wealth 血液分析仪简史和最新进展:可用的检测财富
Pub Date : 2024-06-18 DOI: 10.1515/tjb-2024-0138
Dogan Yucel, M. A. Serdar
{"title":"A brief history of hematology analyzers and recent advancements: the available testing wealth","authors":"Dogan Yucel, M. A. Serdar","doi":"10.1515/tjb-2024-0138","DOIUrl":"https://doi.org/10.1515/tjb-2024-0138","url":null,"abstract":"","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"20 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Determination of molecular pathways and gene ontology of genes associated with Raynaud’s phenomenon 确定雷诺现象相关基因的分子通路和基因本体论
Pub Date : 2024-06-17 DOI: 10.1515/tjb-2023-0197
Gözde Öztan
Abstract Objectives Raynaud’s phenomenon (RF) is a disease that causes discoloration of the fingers. The purpose of this study is to identify the molecular pathways in which genes related to RP illness are involved, as well as uncover the biological processes and molecular functions connected with those genes via the use of gene ontology (GO) analysis. Methods Genes associated with RP in the MalaCards Human Diseases database were detected. Twenty genes obtained from the MalaCards Human Diseases database were included in the study for gene ontology analysis via the STRING database. Accordingly, possible interactions between 20 genes were determined through STRING and network enrichment was performed. Results A significant enrichment by gene ontology enrichment analysis was detected in a subset of genes involved in biological processes including cellular response to luteinizing hormone stimulus, negative regulation of fibrinolysis, negative regulation of smooth muscle cell apoptotic process, plasminogen activation, cellular response to follicle-stimulating hormone stimulus. The assay for molecular function determined enrichment of a subset of genes in chemoattractant activity, growth factor activity, heparin binding, sulfur compound binding, growth factor receptor binding. Through the use of KEGG pathways, we were able to identify many molecular processes that contribute to RP, including the AGE-RAGE signaling pathway in diabetic complications, complement and coagulation cascades, fluid shear stress, atherosclerosis. Conclusions Some individuals may have a genetic predisposition to the onset of Raynaud’s phenomenon. Our data showed that it is associated with genes involved in vascular damage and fibrosis, especially in RP. Therefore, we can include RP disease in the group of vascular diseases.
摘要 目的 雷诺现象(Raynaud's phenomenon,RF)是一种导致手指变色的疾病。本研究旨在通过基因本体(GO)分析,确定雷诺氏病相关基因参与的分子通路,并揭示与这些基因相关的生物学过程和分子功能。方法 在 MalaCards 人类疾病数据库中检测与 RP 相关的基因。研究通过 STRING 数据库对从 MalaCards 人类疾病数据库中获得的 20 个基因进行了基因本体分析。因此,通过 STRING 确定了 20 个基因之间可能存在的相互作用,并进行了网络富集。结果 通过基因本体富集分析,发现涉及细胞对黄体生成素刺激的反应、纤维蛋白溶解的负调控、平滑肌细胞凋亡过程的负调控、纤溶酶原激活、细胞对卵泡刺激素刺激的反应等生物过程的基因子集有明显的富集。分子功能检测确定了化合吸引剂活性、生长因子活性、肝素结合、硫化合物结合、生长因子受体结合等方面的基因子集富集。通过使用 KEGG 通路,我们能够确定许多导致 RP 的分子过程,包括糖尿病并发症中的 AGE-RAGE 信号通路、补体和凝血级联、流体剪切应力、动脉粥样硬化。结论 某些人可能具有雷诺现象发病的遗传易感性。我们的数据显示,雷诺现象与涉及血管损伤和纤维化的基因有关,特别是在雷诺氏病中。因此,我们可以将雷诺氏病纳入血管疾病的范畴。
{"title":"Determination of molecular pathways and gene ontology of genes associated with Raynaud’s phenomenon","authors":"Gözde Öztan","doi":"10.1515/tjb-2023-0197","DOIUrl":"https://doi.org/10.1515/tjb-2023-0197","url":null,"abstract":"Abstract Objectives Raynaud’s phenomenon (RF) is a disease that causes discoloration of the fingers. The purpose of this study is to identify the molecular pathways in which genes related to RP illness are involved, as well as uncover the biological processes and molecular functions connected with those genes via the use of gene ontology (GO) analysis. Methods Genes associated with RP in the MalaCards Human Diseases database were detected. Twenty genes obtained from the MalaCards Human Diseases database were included in the study for gene ontology analysis via the STRING database. Accordingly, possible interactions between 20 genes were determined through STRING and network enrichment was performed. Results A significant enrichment by gene ontology enrichment analysis was detected in a subset of genes involved in biological processes including cellular response to luteinizing hormone stimulus, negative regulation of fibrinolysis, negative regulation of smooth muscle cell apoptotic process, plasminogen activation, cellular response to follicle-stimulating hormone stimulus. The assay for molecular function determined enrichment of a subset of genes in chemoattractant activity, growth factor activity, heparin binding, sulfur compound binding, growth factor receptor binding. Through the use of KEGG pathways, we were able to identify many molecular processes that contribute to RP, including the AGE-RAGE signaling pathway in diabetic complications, complement and coagulation cascades, fluid shear stress, atherosclerosis. Conclusions Some individuals may have a genetic predisposition to the onset of Raynaud’s phenomenon. Our data showed that it is associated with genes involved in vascular damage and fibrosis, especially in RP. Therefore, we can include RP disease in the group of vascular diseases.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"12 35","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141335100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Joint effects of PPARG-C161T (rs3856806) polymorphism and cardiovascular risk factors on restenosis risk after coronary stent implantation PPARG-C161T (rs3856806) 多态性和心血管风险因素对冠状动脉支架植入术后再狭窄风险的共同影响
Pub Date : 2024-06-14 DOI: 10.1515/tjb-2024-0021
Z. Javadova, Fatih Yanar, E. Aslan, G. Ozkara, Fidan Malikova, Onur Kılıcarslan, O. Ser, Ahmet Yildiz, O. Kucukhuseyin, O. Ozturk, Hülya YILMAZ AYDOĞAN
Abstract Objectives The peroxisome proliferator-activated receptor gamma (PPARG) C161T polymorphism (rs3856806) may be a risk factor for in-stent restenosis (ISR) due to its known associations with type 2 diabetes (T2DM), obesity, and coronary artery disease (CAD). This study aims to investigate the relationship between PPARG-C161T polymorphism and the risk of ISR, considering clinical features. Methods According to the results of coronary angiography, the patients who had undergone drug-eluting stent implantation were categorized into two groups: ISR (n=116) and non-ISR (n=265). The control group consisted of 140 healthy subjects with asymptomatic for CAD or any systemic disease. PPARG-C161T genotypes were determined using the real-time polymerase chain reaction melting curve analysis. Results T2DM, hypertension, and hyperlipidemia were observed as the main clinical features causing non-ISR and ISR. The 161-CC genotype was associated with an increased risk of ISR compared to both controls (p=0.014) and non-ISR patients (p=0.008). This difference remained statistically significant after multivariate analysis for non-ISR patients (p=0.003) but not for the ISR group. The prevalence of hypertension and hyperlipidemia was higher in ISR patients with T2DM than in non-ISR patients with T2DM (p=0.002 and p=0.009, respectively). Multivariate logistic regression analysis in subgroups based on the presence of T2DM showed that hypertension (p<0.001) was associated with ISR in patients with T2DM. Conclusions This study points out the association between the PPARG 161-CC genotype and the risk of ISR, which also means that the PPARG 161-T allele is protective against ISR. However, this effect could be divergent in the presence of the metabolic components of the restenosis phenotype, especially T2DM.
摘要 目的 过氧化物酶体增殖激活受体γ(PPARG)C161T多态性(rs3856806)可能是支架内再狭窄(ISR)的危险因素,因为它与2型糖尿病(T2DM)、肥胖和冠状动脉疾病(CAD)有已知的关联。本研究旨在结合临床特征,探讨 PPARG-C161T 多态性与 ISR 风险之间的关系。方法 根据冠状动脉造影结果,将接受药物洗脱支架植入术的患者分为两组:ISR组(116人)和非ISR组(265人)。对照组由 140 名无 CAD 症状或任何系统疾病的健康受试者组成。PPARG-C161T 基因型通过实时聚合酶链反应熔解曲线分析确定。结果 观察到 T2DM、高血压和高脂血症是导致非 ISR 和 ISR 的主要临床特征。与对照组(P=0.014)和非 ISR 患者(P=0.008)相比,161-CC 基因型与 ISR 风险增加有关。对非 ISR 患者进行多变量分析后,这一差异仍具有统计学意义(p=0.003),但对 ISR 组则没有意义。患有 T2DM 的 ISR 患者的高血压和高脂血症患病率高于患有 T2DM 的非 ISR 患者(分别为 p=0.002 和 p=0.009)。根据是否存在 T2DM 进行分组的多变量逻辑回归分析表明,高血压(p<0.001)与 T2DM 患者的 ISR 相关。结论 本研究指出 PPARG 161-CC 基因型与 ISR 风险之间存在关联,这也意味着 PPARG 161-T 等位基因对 ISR 具有保护作用。然而,如果存在再狭窄表型的代谢成分,尤其是 T2DM,这种效应可能会出现偏差。
{"title":"Joint effects of PPARG-C161T (rs3856806) polymorphism and cardiovascular risk factors on restenosis risk after coronary stent implantation","authors":"Z. Javadova, Fatih Yanar, E. Aslan, G. Ozkara, Fidan Malikova, Onur Kılıcarslan, O. Ser, Ahmet Yildiz, O. Kucukhuseyin, O. Ozturk, Hülya YILMAZ AYDOĞAN","doi":"10.1515/tjb-2024-0021","DOIUrl":"https://doi.org/10.1515/tjb-2024-0021","url":null,"abstract":"Abstract Objectives The peroxisome proliferator-activated receptor gamma (PPARG) C161T polymorphism (rs3856806) may be a risk factor for in-stent restenosis (ISR) due to its known associations with type 2 diabetes (T2DM), obesity, and coronary artery disease (CAD). This study aims to investigate the relationship between PPARG-C161T polymorphism and the risk of ISR, considering clinical features. Methods According to the results of coronary angiography, the patients who had undergone drug-eluting stent implantation were categorized into two groups: ISR (n=116) and non-ISR (n=265). The control group consisted of 140 healthy subjects with asymptomatic for CAD or any systemic disease. PPARG-C161T genotypes were determined using the real-time polymerase chain reaction melting curve analysis. Results T2DM, hypertension, and hyperlipidemia were observed as the main clinical features causing non-ISR and ISR. The 161-CC genotype was associated with an increased risk of ISR compared to both controls (p=0.014) and non-ISR patients (p=0.008). This difference remained statistically significant after multivariate analysis for non-ISR patients (p=0.003) but not for the ISR group. The prevalence of hypertension and hyperlipidemia was higher in ISR patients with T2DM than in non-ISR patients with T2DM (p=0.002 and p=0.009, respectively). Multivariate logistic regression analysis in subgroups based on the presence of T2DM showed that hypertension (p<0.001) was associated with ISR in patients with T2DM. Conclusions This study points out the association between the PPARG 161-CC genotype and the risk of ISR, which also means that the PPARG 161-T allele is protective against ISR. However, this effect could be divergent in the presence of the metabolic components of the restenosis phenotype, especially T2DM.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"31 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141340405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of curcumin on PI3K/Akt and AMPK pathways in insulin resistance induced by fructose 姜黄素对果糖诱导的胰岛素抵抗中 PI3K/Akt 和 AMPK 通路的影响
Pub Date : 2024-06-14 DOI: 10.1515/tjb-2024-0027
Gülce Kiren, Ç. Severcan, Suzan Muratoğlu Severcan, Hatice Paşaoğlu
Abstract Objectives Excessive fructose consumption is recognized to elevate insulin resistance in animals and humans. In our study, we aimed to assess the possible consequences of curcumin (curc) treatment applied to rat models of fructose-induced insulin resistance on adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathways in skeletal muscle and adipose tissue. Methods We established four distinct rat groups: corn oil (negative control group), 20 % fructose (positive control group), 20 % fructose and 100 mg/kg curc (100 mg/kg curc group), and 20 % fructose and 200 mg/kg curc (200 mg/kg curc group). The ELISA method was used to determine serum insulin levels, an auto-analyzer was used to measure serum glucose levels, and homeostatic model assessment of insulin resistance (HOMA-IR) values were calculated. In the rat’s skeletal muscle and adipose tissues, the ELISA method was used to determine the following parameters: insulin receptor substrate-1 (IRS-1), phosphorylated insulin receptor substrate-1 (p-IRS-1), PI3K, phosphatidylinositol 3,4,5-trisphosphate (PIP3), phosphoinositide-dependent kinases (PDK-1), phosphorylated Akt (p-Akt), AMPK and glucose transporter type 4 (GLUT4) levels. Results The positive control group exhibited a significant increase in serum glucose, insulin, and HOMA-IR levels, confirming the establishment of the insulin resistance model. In the curcumin dose groups, these values significantly decreased. Additionally, compared to the positive control groups, curcumin dose groups demonstrated a significant increase in the parameters of the Akt/PI3K pathway, AMPK activation, and GLUT4 levels in skeletal muscle and adipose tissues. Conclusions We observed that curcumin demonstrates potential ameliorative effects on the insulin signaling pathway through PI3K/Akt and AMPK pathways.
摘要 目的 人们认识到,摄入过量果糖会增加动物和人类的胰岛素抵抗。在我们的研究中,我们旨在评估姜黄素(curc)治疗果糖诱导的胰岛素抵抗大鼠模型对骨骼肌和脂肪组织中单磷酸腺苷激活蛋白激酶(AMPK)和磷脂酰肌醇-3 激酶(PI3K)/蛋白激酶 B(Akt)通路可能产生的影响。方法 我们设立了四个不同的大鼠组:玉米油组(阴性对照组)、20%果糖组(阳性对照组)、20%果糖和 100 mg/kg curc 组(100 mg/kg curc 组)以及 20% 果糖和 200 mg/kg curc 组(200 mg/kg curc 组)。采用 ELISA 法测定血清胰岛素水平,采用自动分析仪测量血清葡萄糖水平,并计算胰岛素抵抗的稳态模型评估(HOMA-IR)值。用酶联免疫吸附法测定大鼠骨骼肌和脂肪组织中的以下参数:胰岛素受体底物-1(IRS-1)、磷酸化胰岛素受体底物-1(p-IRS-1)、PI3K、磷脂酰肌醇 3,4,5-三磷酸(PIP3)、磷脂酰肌醇依赖性激酶(PDK-1)、磷酸化 Akt(p-Akt)、AMPK 和葡萄糖转运体 4 型(GLUT4)水平。结果 阳性对照组的血清葡萄糖、胰岛素和 HOMA-IR 水平明显升高,证实了胰岛素抵抗模型的建立。在姜黄素剂量组中,这些数值明显下降。此外,与阳性对照组相比,姜黄素剂量组在骨骼肌和脂肪组织中的 Akt/PI3K 通路参数、AMPK 激活和 GLUT4 水平均有显著增加。结论 我们观察到姜黄素通过 PI3K/Akt 和 AMPK 通路对胰岛素信号通路具有潜在的改善作用。
{"title":"The effect of curcumin on PI3K/Akt and AMPK pathways in insulin resistance induced by fructose","authors":"Gülce Kiren, Ç. Severcan, Suzan Muratoğlu Severcan, Hatice Paşaoğlu","doi":"10.1515/tjb-2024-0027","DOIUrl":"https://doi.org/10.1515/tjb-2024-0027","url":null,"abstract":"Abstract Objectives Excessive fructose consumption is recognized to elevate insulin resistance in animals and humans. In our study, we aimed to assess the possible consequences of curcumin (curc) treatment applied to rat models of fructose-induced insulin resistance on adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathways in skeletal muscle and adipose tissue. Methods We established four distinct rat groups: corn oil (negative control group), 20 % fructose (positive control group), 20 % fructose and 100 mg/kg curc (100 mg/kg curc group), and 20 % fructose and 200 mg/kg curc (200 mg/kg curc group). The ELISA method was used to determine serum insulin levels, an auto-analyzer was used to measure serum glucose levels, and homeostatic model assessment of insulin resistance (HOMA-IR) values were calculated. In the rat’s skeletal muscle and adipose tissues, the ELISA method was used to determine the following parameters: insulin receptor substrate-1 (IRS-1), phosphorylated insulin receptor substrate-1 (p-IRS-1), PI3K, phosphatidylinositol 3,4,5-trisphosphate (PIP3), phosphoinositide-dependent kinases (PDK-1), phosphorylated Akt (p-Akt), AMPK and glucose transporter type 4 (GLUT4) levels. Results The positive control group exhibited a significant increase in serum glucose, insulin, and HOMA-IR levels, confirming the establishment of the insulin resistance model. In the curcumin dose groups, these values significantly decreased. Additionally, compared to the positive control groups, curcumin dose groups demonstrated a significant increase in the parameters of the Akt/PI3K pathway, AMPK activation, and GLUT4 levels in skeletal muscle and adipose tissues. Conclusions We observed that curcumin demonstrates potential ameliorative effects on the insulin signaling pathway through PI3K/Akt and AMPK pathways.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"1 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141341143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of adropin indices and PCSK9 in non-diabetic men with severe obstructive sleep apnea 评估患有严重阻塞性睡眠呼吸暂停的非糖尿病男性的阿托品指数和 PCSK9
Pub Date : 2024-06-04 DOI: 10.1515/tjb-2023-0283
Levent Deniz, H. Aral, Özlem Akdoğan, H. Arslan, E. Yiğit
We aimed to investigate the relationship among proprotein convertase subtilisin/kexin type 9 (PCSK9), adropin levels, inflammation, and sleep variables in non-diabetic males with severe obstructive sleep apnea (OSA). This cross-sectional study included adults aged 18 to 65 who underwent polysomnography due to sleep problems between July 2019 and August 2020. Participants were grouped based on their apnea-hypopnea index (AHI). We included 32 males with simple snoring (AHI<5 events/h) as the controls and 48 males with severe OSA (AHI≥30 events/h). Furthermore, patients with severe OSA were divided into two groups based on body mass index (BMI), resulting in three groups in total. Adropin and PCSK9 were analyzed using the enzyme-linked immunosorbent assay method. In severe OSA with BMI≥30 kg/m2, compared to the controls, blood pressure values, interleukin-6 (IL-6), white blood cell (WBC) count, systemic inflammation response index, neutrophil, monocyte counts were found to be higher, but adropin/BMI, adropin/waist circumference, adropin/neck circumference were significantly lower. Adropin/BMI had the highest correlation coefficient with IL-6. Although there was no significant difference in PCSK9 levels among the groups, PCSK9 was independently correlated with the WBC and its subsets. Our study is of clinical importance as it is the first to show a relationship between PCSK9 and inflammation markers in severe OSA. Also, this study demonstrated the potential value of adropin, in combination with BMI, as a valuable indicator for assessing inflammation and OSA severity.
我们的目的是研究患有严重阻塞性睡眠呼吸暂停(OSA)的非糖尿病男性患者中,丙蛋白转换酶亚基酶/kexin 9型(PCSK9)、阿托品水平、炎症和睡眠变量之间的关系。 这项横断面研究纳入了2019年7月至2020年8月期间因睡眠问题接受多导睡眠图检查的18至65岁成年人。根据呼吸暂停-低通气指数(AHI)对参与者进行分组。我们将32名单纯打鼾(AHI<5次/小时)的男性作为对照组,将48名严重OSA(AHI≥30次/小时)的男性作为对照组。此外,根据体重指数(BMI)将严重 OSA 患者分为两组,共三组。采用酶联免疫吸附法分析阿托品和PCSK9。 与对照组相比,BMI≥30 kg/m2的重度OSA患者的血压值、白细胞介素-6(IL-6)、白细胞计数、全身炎症反应指数、中性粒细胞、单核细胞计数均高于对照组,但阿托品/BMI、阿托品/腰围、阿托品/颈围均显著低于对照组。阿托品/体重指数与 IL-6 的相关系数最高。虽然各组间的 PCSK9 水平无明显差异,但 PCSK9 与白细胞及其亚群独立相关。 我们的研究首次显示了严重 OSA 患者 PCSK9 与炎症指标之间的关系,因此具有重要的临床意义。此外,这项研究还证明了阿托品与体重指数相结合作为评估炎症和 OSA 严重程度的重要指标的潜在价值。
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Turkish Journal of Biochemistry
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