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Differential effects of choline on TLR2/4 mediated signaling through possible regulation of toll-interacting protein in hepatocellular carcinoma cell lines 胆碱通过可能调节肝癌细胞系中的 toll-interacting 蛋白,对 TLR2/4 介导的信号传导产生不同影响
Pub Date : 2024-05-27 DOI: 10.1515/tjb-2023-0282
Elif Baris, Ayse Banu Demir
Toll-like receptor (TLR) mediated inflammatory status plays an important role in development and progression of hepatocellular carcinoma (HCC). Toll-interacting protein (TOLLIP) has an inhibitory effect on TLR-mediated inflammatory signalling and expression profile of TOLLIP varies between malignancies including HCC. Cholinergic anti-inflammatory pathway (CAP) is an endogenous mechanism that controls inflammatory status via α7nicotinic acetylcholine receptors (α7nAChR). This study aims to investigate the effect of CAP-acting agent choline on TOLLIP and its related TLR-mediated inflammatory response in HCC cells with distinct differentiation stages. The expression patterns of α7nAChR, TLR2/4, TOLLIP, IL6,NFkB genes were evaluated by RT-PCR and ELISA in the presence of choline, along with the real-time cell proliferation and migration in HEP3B and SNU449 HCC cell lines. The interaction between choline and TOLLIP assessed by using in-silico analyses. Choline downregulated TOLLIP in Hep3B and SNU449 cells. However, the expressions of α7nAChR, NF-κB, IL-6, TLR2 and TLR4 showed a decreased pattern in well differentiated HEP3B cells, while an increased pattern in poorly differentiated SNU449 cells. Choline might exert differential effects in TLR2/4-dependent signalling based on the differentiation stages of the HCC cells, suggesting its potential therapeutic effects in earlier stages of HCC which might be result of its partial modulation of TOLLIP.
Toll样受体(TLR)介导的炎症状态在肝细胞癌(HCC)的发生和发展中起着重要作用。Toll-interacting蛋白(TOLLIP)对TLR介导的炎症信号有抑制作用,不同恶性肿瘤(包括HCC)的TOLLIP表达情况各不相同。胆碱能抗炎通路(CAP)是一种通过α7烟碱乙酰胆碱受体(α7nAChR)控制炎症状态的内源性机制。本研究旨在探讨 CAP 作用剂胆碱对不同分化阶段的 HCC 细胞中 TOLLIP 及其相关 TLR 介导的炎症反应的影响。 研究采用 RT-PCR 和 ELISA 方法评估了胆碱存在时 HEP3B 和 SNU449 HCC 细胞系中 α7nAChR、TLR2/4、TOLLIP、IL6、NFkB 基因的表达模式,以及实时细胞增殖和迁移情况。通过体内分析评估了胆碱与 TOLLIP 之间的相互作用。 胆碱下调了 Hep3B 和 SNU449 细胞中的 TOLLIP。然而,在分化良好的 HEP3B 细胞中,α7nAChR、NF-κB、IL-6、TLR2 和 TLR4 的表达呈下降趋势,而在分化不良的 SNU449 细胞中则呈上升趋势。 胆碱可能会根据 HCC 细胞的分化阶段对 TLR2/4 依赖性信号产生不同的影响,这表明胆碱对早期 HCC 有潜在的治疗作用,这可能是胆碱部分调节 TOLLIP 的结果。
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引用次数: 0
Effectiveness after immunization with BNT162b2 and Gam-COVID-Vac for SARS-CoV-2 and neutralizing antibody titers in health care workers 用 BNT162b2 和 Gam-COVID-Vac 免疫 SARS-CoV-2 后的效果以及医护人员的中和抗体滴度
Pub Date : 2024-05-24 DOI: 10.1515/tjb-2023-0213
M. Emin, D. Cibrev, Coskun Kerala, D. Petrovska-Cvetkovska, Valdrina Ajeti, H. Ampova, I. Kostovska, K. Tosheska-Trajkovska
The aim of this study was to describe the effectiveness of the vaccines (Tozinameran and Sputnik V), administered on a convenience sample of healthcare workers, and also to describe the relationship between the levels of neutralizing antibodies (NAbs) and the type of vaccine used, as well as their association with incident cases during follow-up. The study included 262 participants, who underwent vaccination during the period from September 2021 until August 2022. For determining the levels of NAbs we used the CLIA based method, and all the samples were processed with the SNIBE Maglumi 800 analyzer. The patients were observed for one year for occurrence of incident infection. The participants with prior SARS-CoV-2 positivity showed substantially higher titer of NAbs (8.86 vs. 0.94, p<0.001). The participants in the Gam-COVID-Vac group had median levels of NAbs of 1.57 (IQR 0.42–5.73), while they in the Tozinameran group showed substantially higher levels of 2.37 (IQR 0.9–6.27). The incident cases after immunization had substantially lower median values of NAbs when compared to the rest (0.48 vs. 3.97, p<0.001), and the interval between the second dose and the serological measurements were similar. The current study showed that the tested vaccines demonstrated vaccine effectiveness of over 50 % during the first year after the vaccination in a sample of health care workers. Although health care workers remain separate population group, when compared to the rest, the results could be extrapolated to populations with similar age and immune experience.
本研究的目的是描述在方便抽样的医疗工作者中接种的疫苗(Tozinameran 和 Sputnik V)的有效性,同时描述中和抗体(NAbs)水平与所用疫苗类型之间的关系,以及它们与随访期间发生的病例之间的关联。 这项研究包括 262 名参与者,他们在 2021 年 9 月至 2022 年 8 月期间接种了疫苗。我们采用基于 CLIA 的方法来确定 NAbs 的水平,所有样本均使用 SNIBE Maglumi 800 分析仪进行处理。我们对患者进行了为期一年的观察,以确定是否发生感染。 曾出现过 SARS-CoV-2 阳性的参与者的 NAbs 滴度要高得多(8.86 对 0.94,P<0.001)。Gam-COVID-Vac 组参与者的 NAbs 中位数为 1.57(IQR 0.42-5.73),而 Tozinameran 组参与者的 NAbs 中位数则高达 2.37(IQR 0.9-6.27)。免疫接种后的病例与其他病例相比,NAbs 的中位值要低得多(0.48 vs. 3.97,p<0.001),而且第二次接种与血清学测量之间的间隔时间相似。 目前的研究表明,在医护人员样本中,测试的疫苗在接种后第一年的疫苗有效性超过 50%。尽管医护人员仍然是一个独立的人群,但与其他人群相比,研究结果可以推广到具有相似年龄和免疫经验的人群中。
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引用次数: 0
Frequency and pattern of test utilization rate in clinical biochemistry laboratory: two different large hospital examples 临床生化实验室检验使用率的频率和模式:两家不同的大型医院实例
Pub Date : 2024-05-21 DOI: 10.1515/tjb-2023-0099
Ali Yalçındağ, Fevzi Nuri Aydın, Özben Özden Işıklar, Fatmagül Can, Murat Karademir, Ersen Uzunal, A. O. Akyurek, Doğan Yücel, M. A. Serdar
Clinical Biochemistry Laboratories (CBL) are the most frequently utilized laboratory group in healthcare, and their significance in patient care is indisputable. This study investigated the frequency and pattern of test utilization rate in CBL at two large hospitals’ outpatient and inpatient clinics. A total of 43,732,428 CBL tests, including clinical chemistry, immunoassay, coagulation, specific proteins, CBC, and urinalysis, were conducted for 12,182,382 patients across two large hospitals in different settings between 2018 and 2022. These tests were analyzed alongside patient admissions data, with a focus on the distribution across various clinics. 94 and 93 % of those admitted to Hospitals 1 and 2 were outpatients. They had applied to CBL laboratories for 27.1–30.3 % of outpatients and 81.2–88.7 % of inpatients for at least one test. When analyzing the rates at which laboratory tests were requested for outpatients, it was found that emergency departments had the highest test-requesting rates, ranging from 19.99 to 45.36 %. This was followed by internal medicine clinics, with rates ranging from 13.77 to 14.8 %, and inpatient intensive care units, with rates between 24.31 and 30.14 %. Outpatients had 10–11 test requests for each patient and 16–31 for inpatients. The most frequently requested laboratory tests were CBC, glucose, creatinine, urea, AST and ALT in two hospitals. Despite significant variations in location, structure, medical staff, and patient demographics, approximately one-third of outpatients and 85 % of inpatients at these hospitals undergo testing in CBL. CBLs are essential for screening, diagnosis, prognosis, and healthcare treatment.
临床生化实验室(CBL)是医疗保健领域使用最频繁的实验室群,其在患者护理方面的重要性毋庸置疑。本研究调查了两家大型医院门诊和住院部生化实验室的化验使用频率和模式。 在2018年至2022年期间,两家大型医院在不同的环境中为12182382名患者共进行了43732428项CBL检测,包括临床化学、免疫测定、凝血、特异性蛋白、全血细胞计数和尿液分析。在分析这些检测项目的同时,还分析了患者的入院数据,重点关注其在不同诊室的分布情况。 第一医院和第二医院分别收治了 94% 和 93% 的门诊病人。27.1%-30.3%的门诊病人和81.2%-88.7%的住院病人至少向 CBL 实验室申请过一次化验。在分析门诊病人的化验申请率时发现,急诊科的化验申请率最高,从19.99%到45.36%不等。紧随其后的是内科门诊,申请率为 13.77% 至 14.8%,住院重症监护室的申请率为 24.31% 至 30.14%。门诊病人的化验申请为 10-11 次/人,住院病人的化验申请为 16-31 次/人。两家医院最常要求的化验项目是全血细胞计数、血糖、肌酐、尿素、谷草转氨酶和谷丙转氨酶。 尽管这些医院在地点、结构、医务人员和患者人口统计学方面存在很大差异,但仍有大约三分之一的门诊患者和 85% 的住院患者在 CBL 接受检验。CBL 对筛查、诊断、预后和医疗保健治疗至关重要。
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引用次数: 0
Does COVID-19 infection alter serum biochemical and hematological biomarkers in deceased dementia patients? COVID-19 感染是否会改变已故痴呆症患者的血清生化和血液生物标志物?
Pub Date : 2024-05-20 DOI: 10.1515/tjb-2022-0206
D. Aydemir, Muammer Yucel, Mehmet Koseoglu, N. N. Ulusu
The elderly population is categorized as a risk group for COVID-19 infection, and dementia is the primary cause of disability in elderly individuals and affects 70 % of the elderly population. In this study, we evaluated the blood and serum biomarkers of deceased dementia patients infected by COVID-19 compared to the survived dementia and non-dementia patients. Laboratory biomarkers of 11 dementia patients infected by COVID-19 have been used for this study. The five patients’ serum biochemistry and blood data were compared with the six patients who died because of COVID-19. Additionally, data from nine patients aged 85–96 infected with COVID-19 without dementia have been used to compare the difference between dementia and non-dementia individuals. D-dimer, C-reactive protein (CRP), glucose, blood urea nitrogen (BUN), alanine transaminase (ALT), aspartate aminotransferase (AST), troponin, procalcitonin, red cell distribution width (RDW), white blood cell (WBC), neutrophil (NEU) and %NEU levels significantly increased in the deceased dementia patients compared to the survived and non-dementia individuals. Calcium (Ca), hematocrit (HCT), red blood cells (RBC), lymphocyte (%LYM), monocyte %MONO, and basophil (%BASO) levels significantly decreased in the deceased dementia patients compared to the survived and non-dementia individuals infected by COVID-19. Serum biochemistry and hematological biomarkers, including D-dimer, CRP, glucose, ALT, AST, BUN, troponin, procalcitonin, RDW, RBC, WBC, NEU, %NEU, Ca, HCT, %LYM, %MONO, and %BASO were significantly altered in deceased dementia patients infected by COVID-19 compared to the survived individuals.
老年人群被列为 COVID-19 感染的高危人群,而痴呆症是导致老年人残疾的主要原因,影响着 70% 的老年人群。在这项研究中,我们评估了感染 COVID-19 的已故痴呆症患者的血液和血清生物标志物,并与存活的痴呆症患者和非痴呆症患者进行了比较。 本研究使用了 11 名感染 COVID-19 的痴呆症患者的实验室生物标志物。五名患者的血清生化和血液数据与六名因 COVID-19 而死亡的患者进行了比较。此外,本研究还使用了九名 85-96 岁感染 COVID-19 但未患痴呆症的患者的数据,以比较痴呆症患者与非痴呆症患者之间的差异。 与存活和未患痴呆症的患者相比,已故痴呆症患者的 D-二聚体、C 反应蛋白 (CRP)、葡萄糖、血尿素氮 (BUN)、丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)、肌钙蛋白、降钙素原、红细胞分布宽度 (RDW)、白细胞 (WBC)、中性粒细胞 (NEU) 和 %NEU 水平明显升高。与受 COVID-19 感染的存活者和非痴呆症患者相比,已故痴呆症患者的钙(Ca)、血细胞比容(HCT)、红细胞(RBC)、淋巴细胞(%LYM)、单核细胞(%MONO)和嗜碱性粒细胞(%BASO)水平明显下降。 受 COVID-19 感染的已故痴呆症患者的血清生化和血液生物标志物,包括 D-二聚体、CRP、葡萄糖、ALT、AST、BUN、肌钙蛋白、降钙素原、RDW、RBC、WBC、NEU、%NEU、Ca、HCT、%LYM、%MONO 和 %BASO 与存活者相比发生了明显变化。
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引用次数: 0
Correlation between serum 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D in response to analytical procedures; a systematic review and meta-analysis 血清中 1,25-二羟基维生素 D 与 25-羟基维生素 D 之间的相关性对分析程序的影响;系统回顾和荟萃分析
Pub Date : 2024-05-13 DOI: 10.1515/tjb-2023-0258
M. A. Serdar, Fatma Demet Arslan, N. Y. Saral, Doğan Yücel
In this study, the aim is to provide a more detailed understanding of vitamin D metabolism by evaluating the correlation between 1,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D) according to the variations in measurement methods and clinical conditions. We searched PubMed, Embase, and Web of Science for studies reporting correlation results between 1,25(OH)2D and 25(OH)D. We performed a meta-analysis based on the correlation results of 1,25(OH)2D and 25(OH)D in different clinical conditions. We included a total of 63 studies and our laboratory’s results in the meta-analysis. The studies were categorized into high-quality methods group (HQMG), medium-quality methods group (MQMG), and low-quality methods group (LQMG) based on the 25(OH)D and 1,25(OH)2D measurement. In the healthy, renal disease, and other disease groups, the highest correlation values were observed in the studies categorized as HQMG, with values of 0.35 (95 % CI; 0.23–0.48), 0.36 (95 % CI; 0.26–0.42), and 0.36 (95 % CI; 0.22–0.48), respectively. Significant statistical heterogeneity was observed in the healthy, renal disease, and other disease groups, with I2 values of 92.4 , 82.7, and 90.7 %, respectively (p<0.001). Both Funnel plots and the results of Egger’s and Begg’s tests indicated no statistically significant bias across all studies. A significantly low correlation was found between 25(OH)D and 1,25(OH)2D. However, higher correlations were found in the studies categorized as HQMG. Various factors, including methodological inadequacies and disparities, might contribute to this. In the future, with more accurate and reproducible measurements of 1,25(OH)2D, a clearer understanding of vitamin D metabolism will be achieved.
本研究旨在根据测量方法和临床条件的不同,评估 1,25-二羟基维生素 D(1,25(OH)2D)和 25-羟基维生素 D(25(OH)D)之间的相关性,从而更详细地了解维生素 D 代谢。 我们在 PubMed、Embase 和 Web of Science 中检索了报告 1,25(OH)2D 和 25(OH)D 相关性结果的研究。我们根据 1,25(OH)2D 和 25(OH)D 在不同临床条件下的相关性结果进行了荟萃分析。我们共纳入了 63 项研究和我们实验室的结果进行荟萃分析。根据 25(OH)D 和 1,25(OH)2D的测量结果,这些研究被分为高质量方法组(HQMG)、中等质量方法组(MQMG)和低质量方法组(LQMG)。 在健康组、肾病组和其他疾病组中,被归类为 HQMG 的研究的相关性值最高,分别为 0.35(95 % CI;0.23-0.48)、0.36(95 % CI;0.26-0.42)和 0.36(95 % CI;0.22-0.48)。在健康组、肾病组和其他疾病组中观察到显著的统计学异质性,I2 值分别为 92.4 %、82.7 % 和 90.7 %(P<0.001)。漏斗图以及 Egger 检验和 Begg 检验的结果均表明,所有研究在统计学上均无显着偏倚。 25(OH)D 和 1,25(OH)2D之间的相关性明显较低。然而,在归类为 HQMG 的研究中发现了较高的相关性。包括方法不足和差异在内的各种因素可能是造成这种情况的原因。未来,随着 1,25(OH)2D 测量的更准确和可重复性的提高,人们将对维生素 D 代谢有更清晰的认识。
{"title":"Correlation between serum 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D in response to analytical procedures; a systematic review and meta-analysis","authors":"M. A. Serdar, Fatma Demet Arslan, N. Y. Saral, Doğan Yücel","doi":"10.1515/tjb-2023-0258","DOIUrl":"https://doi.org/10.1515/tjb-2023-0258","url":null,"abstract":"\u0000 \u0000 \u0000 In this study, the aim is to provide a more detailed understanding of vitamin D metabolism by evaluating the correlation between 1,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D) according to the variations in measurement methods and clinical conditions.\u0000 \u0000 \u0000 \u0000 We searched PubMed, Embase, and Web of Science for studies reporting correlation results between 1,25(OH)2D and 25(OH)D. We performed a meta-analysis based on the correlation results of 1,25(OH)2D and 25(OH)D in different clinical conditions. We included a total of 63 studies and our laboratory’s results in the meta-analysis. The studies were categorized into high-quality methods group (HQMG), medium-quality methods group (MQMG), and low-quality methods group (LQMG) based on the 25(OH)D and 1,25(OH)2D measurement.\u0000 \u0000 \u0000 \u0000 In the healthy, renal disease, and other disease groups, the highest correlation values were observed in the studies categorized as HQMG, with values of 0.35 (95 % CI; 0.23–0.48), 0.36 (95 % CI; 0.26–0.42), and 0.36 (95 % CI; 0.22–0.48), respectively. Significant statistical heterogeneity was observed in the healthy, renal disease, and other disease groups, with I2 values of 92.4 , 82.7, and 90.7 %, respectively (p<0.001). Both Funnel plots and the results of Egger’s and Begg’s tests indicated no statistically significant bias across all studies.\u0000 \u0000 \u0000 \u0000 A significantly low correlation was found between 25(OH)D and 1,25(OH)2D. However, higher correlations were found in the studies categorized as HQMG. Various factors, including methodological inadequacies and disparities, might contribute to this. In the future, with more accurate and reproducible measurements of 1,25(OH)2D, a clearer understanding of vitamin D metabolism will be achieved.\u0000","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"41 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140984007","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
Influence of TLR4 signaling on Cannabidiol’s antitumor effectiveness in lung adenocarcinoma cells TLR4 信号对大麻二酚在肺腺癌细胞中抗肿瘤效果的影响
Pub Date : 2024-05-03 DOI: 10.1515/tjb-2023-0256
Demet Kaçaroğlu, Melek Parlak Khalily, Seher Yaylacı
Lung cancer remains a predominant cancer type with high incidence and low survival rates. Key challenges in its treatment include impaired cellular mechanisms, notably resistance to apoptosis and altered immune responses. A critical aspect in this context is the heightened TLR4-mediated signaling, known to promote cell survival, metastasis, and resistance to cell death, particularly impacting immune microenvironment regulation. This study focuses on evaluating the impact of TLR4 signaling activation on potential therapeutic strategies. Our research utilizes Cannabidiol (CBD), a compound already employed in mitigating chemotherapy side effects in lung adenocarcinoma, recognized for its antitumor properties including antiproliferative, antimetastatic, and apoptosis-inducing effects. However, the effectiveness of CBD in lung cancer cells with elevated TLR4 signaling remains uncertain. Our findings reveal that the combination of CBD and TLR4 agonist affects cell viability, proliferation, cell cycle progression, apoptosis, and gene expression related to immune response and extracellular matrix regulation. In lung adenocarcinoma cells with activated TLR4, CBD shows an increased IC50 value, reflecting reduced antiproliferative capacity. Furthermore, its efficacy in arresting the cell cycle and inducing apoptosis is also compromised. The influence on immune response and extracellular matrix regulation is also altered in TLR4-activated cells. These results indicate that TLR4 activation significantly diminishes the antitumor efficacy of CBD. This highlights the importance of considering TLR4 signaling activation in future research on therapeutic agents like CBD for cancer treatment.
肺癌仍然是发病率高、存活率低的主要癌症类型。肺癌治疗面临的主要挑战包括细胞机制受损,特别是对细胞凋亡的抵抗和免疫反应的改变。在这种情况下,一个关键的方面是 TLR4 介导的信号传导增强,众所周知,TLR4 可促进细胞存活、转移和抵抗细胞死亡,特别是影响免疫微环境调控。本研究的重点是评估 TLR4 信号激活对潜在治疗策略的影响。 我们的研究利用了大麻二酚(CBD),这是一种已被用于减轻肺腺癌化疗副作用的化合物,其抗肿瘤特性包括抗增殖、抗转移和诱导细胞凋亡的作用。然而,CBD 对 TLR4 信号升高的肺癌细胞的疗效仍不确定。 我们的研究结果表明,CBD 和 TLR4 激动剂的结合会影响细胞的活力、增殖、细胞周期进展、凋亡以及与免疫反应和细胞外基质调节相关的基因表达。在激活了 TLR4 的肺腺癌细胞中,CBD 的 IC50 值增加,反映出其抗增殖能力降低。此外,其阻止细胞周期和诱导细胞凋亡的功效也受到了影响。在 TLR4 激活的细胞中,对免疫反应和细胞外基质调节的影响也发生了改变。 这些结果表明,TLR4 激活会显著降低 CBD 的抗肿瘤功效。这凸显了在未来研究治疗剂(如用于癌症治疗的 CBD)时考虑 TLR4 信号激活的重要性。
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引用次数: 0
Relationship between methylation pattern of the SYN2 gene and schizophrenia SYN2 基因甲基化模式与精神分裂症的关系
Pub Date : 2024-05-01 DOI: 10.1515/tjb-2023-0249
İbrahim Fettahoğlu, S. Kartalci, H. G. Gözükara Bağ, Ceren Acar
Schizophrenia is a neuropsychiatric disease, and its etiology is not exactly understood. DNA methylation is an important phenomenon that affects the rise of abnormal phenotypes in many cases. Investigation of the association between DNA methylation and schizophrenia is crucial for elucidating the basis of schizophrenia. Previous association studies confirm that the SYN2 gene is a strong candidate gene for schizophrenia. In the current study, the relationship between the methylation status of the SYN2 gene and schizophrenia was investigated. The aim is to obtain crucial results for illuminating the effects of the SYN2 methylation changes in the etiology of schizophrenia. In light of this scientific information, we investigated the methylation status of three different CpG regions in the promoter of the SYN2 gene and compared them in healthy controls and schizophrenia patients. Thirty-three healthy controls and 36 schizophrenia patients were included in this study. Sequencing was performed using the pyrosequencing method to reveal the methylation pattern. As a result of the statistical analysis, it was confirmed that there is a significant relationship between the methylation pattern of the SYN2 gene and schizophrenia. Schizophrenia patients showed more methylation in position 2 and position 3. Additionally, the average methylation ratio is increased in schizophrenia patients. We find an association between the DNA methylation pattern of the SYN2 gene and schizophrenia. These results can help to the understanding of the etiology of schizophrenia. Except for these, DNA methylation changes in the SYN2 gene in people who live in urban and rural areas can be one of the reasons for the different incidences of schizophrenia in these regions.
精神分裂症是一种神经精神疾病,其病因尚不完全清楚。在许多情况下,DNA 甲基化是影响异常表型产生的一个重要现象。研究 DNA 甲基化与精神分裂症之间的关联对于阐明精神分裂症的发病基础至关重要。以往的关联研究证实,SYN2 基因是精神分裂症的一个强有力的候选基因。本研究调查了 SYN2 基因甲基化状态与精神分裂症之间的关系。目的是获得关键性结果,以阐明 SYN2 甲基化变化在精神分裂症病因学中的影响。 根据这些科学信息,我们调查了 SYN2 基因启动子中三个不同 CpG 区域的甲基化状态,并对健康对照组和精神分裂症患者的甲基化状态进行了比较。本研究共纳入 33 名健康对照组和 36 名精神分裂症患者。采用热释光测序法进行测序,以揭示甲基化模式。 统计分析结果证实,SYN2 基因的甲基化模式与精神分裂症之间存在显著关系。精神分裂症患者在第 2 位和第 3 位的甲基化程度更高。此外,精神分裂症患者的平均甲基化比率也有所增加。 我们发现 SYN2 基因的 DNA 甲基化模式与精神分裂症之间存在关联。这些结果有助于了解精神分裂症的病因。除此以外,生活在城市和农村地区的人的 SYN2 基因的 DNA 甲基化变化也可能是这些地区精神分裂症发病率不同的原因之一。
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引用次数: 0
Activity of protein C, protein S and antithrombin 3 in COVID-19 patients treated with different modalities of oxygen supplementation 采用不同补氧方式治疗 COVID-19 患者的蛋白 C、蛋白 S 和抗凝血酶 3 活性
Pub Date : 2024-04-25 DOI: 10.1515/tjb-2023-0119
Šavuk Ana, Grizelj Danijela, Svaguša Tomo, Čulo Melanie-Ivana, Zagorec Nikola, Šakota Sara, Orehovec Biserka, Kelava Tomislav, Livun Ana, Marković Ivan, Baković Josip, Kereš Tatjana
COVID-19 in it is more severe form is characterized by a hyperinflammatory condition, hypercoagulation state and the appearance of pulmonary microembolism. In this study we wanted to correlate levels of D-Dimer, protein C, protein S and antithrombin 3 with severity of disease and clinical outcome. We included 134 of patients who were divided in 3 groups regarding oxygen support (high flow oxygen therapy, mechanical ventilation and oxygen supplementation with nasal cannula or mask). Concentration of D-Dimer, and activity of protein C and antithrombin 3 are presented as mean±SD and differed significantly between patients on mechanical ventilation (3.26 ± 1.15 mg/L, 86 ± 22.55 %, 81.21 ± 17.61 %)/HFNO (2.35 ± 1.68 mg/L, 109.6 ± 26.96 %, 94.67 ± 17.49 %)/BNC (1.37 ± 1.17 mg/L, 116.92 ± 28.16 %, 103.29 ± 15.63 %) with p<0.001 for all parameters. Mortality in oxygen group was 10.9 %, in HFNC group 40.7 % and in mechanical ventilated group 80 %. determination of anticoagulant factors in COVID-19 patients may indicate which of them are at increased risk of developing severe disease, venous thromboembolism and fatal clinical outcome.
更严重的 COVID-19 以高炎症状态、高凝状态和出现肺微栓塞为特征。在这项研究中,我们希望将 D-二聚体、蛋白 C、蛋白 S 和抗凝血酶 3 的水平与疾病的严重程度和临床结果联系起来。 我们将 134 名患者分为三组,分别给予氧支持(高流量氧疗、机械通气和鼻插管或面罩补氧)。 D-Dimer 的浓度、蛋白 C 和抗凝血酶 3 的活性以平均值(±SD)表示,机械通气患者(3.26 ± 1.15 mg/L、86 ± 22.55 %、81.21±17.61%)/HFNO(2.35±1.68 mg/L,109.6±26.96%,94.67±17.49%)/BNC(1.37±1.17 mg/L,116.92±28.16%,103.29±15.63%)之间存在明显差异,所有参数的P<0.001。氧疗组的死亡率为 10.9%,HFNC 组的死亡率为 40.7%,机械通气组的死亡率为 80%。COVID-19 患者抗凝因子的测定可表明哪些患者发生严重疾病、静脉血栓栓塞和致命临床结局的风险增加。
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引用次数: 0
Resveratrol modulates signalling to inhibit vascular smooth muscle cell proliferation induced by angiotensin II and high glucose 白藜芦醇调节信号传递,抑制血管紧张素 II 和高血糖诱导的血管平滑肌细胞增殖
Pub Date : 2024-04-19 DOI: 10.1515/tjb-2023-0191
A. Çetin, Mustafa Kırça, A. Yeşilkaya
The proliferation of vascular smooth muscle cells (VSMCs) induced by hyperglycemia plays a pivotal role in the development of atherosclerosis and restenosis. This study aims to examine the impact of angiotensin II (Ang II) and high glucose on VSMC proliferation and the phosphorylation status of key signalling proteins, specifically ERK1/2, Akt, and STAT3. Furthermore, we assess the inhibitory effects of resveratrol, a polyphenolic compound, on these signalling pathways. Primary vascular smooth muscle cells (VSMCs) isolated from rat aortas were cultured in both standard media (SM: 5.5 mM) and high glucose media (HGM: 25 mM) and then treated with Ang II (100 nM). Proliferation was assessed using the WST-1 assay, and protein analysis was performed through immunoblotting. Ang II increased VSMC proliferation by 39 % in standard glucose environments and 17 % in high glucose environments. Resveratrol effectively suppressed Ang II-induced VSMC proliferation in both media. Furthermore, resveratrol inhibited the phosphorylation of ERK1/2 and Akt. Ang II also induced STAT3 phosphorylation by 29 and 18.5 % in SM and HGM, respectively. However, resveratrol treatment reduced STAT3 phosphorylation to control levels. These findings demonstrated that resveratrol reduces VSMC proliferation induced by Ang II and high glucose conditions, exerting its inhibitory effects by suppressing ERK1/2, Akt, and STAT3 phosphorylation. These results provide valuable insights into the cardioprotective properties of resveratrol.
高血糖诱导的血管平滑肌细胞(VSMC)增殖在动脉粥样硬化和再狭窄的发展中起着关键作用。本研究旨在探讨血管紧张素 II(Ang II)和高血糖对血管平滑肌细胞增殖和关键信号蛋白(特别是 ERK1/2、Akt 和 STAT3)磷酸化状态的影响。此外,我们还评估了多酚化合物白藜芦醇对这些信号通路的抑制作用。 从大鼠主动脉分离的原代血管平滑肌细胞(VSMC)在标准培养基(SM:5.5 mM)和高葡萄糖培养基(HGM:25 mM)中培养,然后用 Ang II(100 nM)处理。用 WST-1 试验评估增殖情况,并通过免疫印迹进行蛋白质分析。 在标准葡萄糖环境中,Ang II 使血管内皮细胞增殖增加了 39%,在高糖环境中增加了 17%。白藜芦醇能有效抑制 Ang II 诱导的血管内皮细胞增殖。此外,白藜芦醇还抑制了 ERK1/2 和 Akt 的磷酸化。在 SM 和 HGM 中,Ang II 还分别诱导 STAT3 磷酸化 29% 和 18.5%。然而,白藜芦醇处理可将 STAT3 磷酸化降至控制水平。 这些研究结果表明,白藜芦醇通过抑制 ERK1/2、Akt 和 STAT3 磷酸化,减少了 Ang II 和高血糖条件下诱导的血管内皮细胞增殖。这些结果为白藜芦醇的心脏保护特性提供了宝贵的见解。
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引用次数: 0
Cytotoxic and apoptotic effectiveness of Cypriot honeybee (Apis mellifera cypria) venom on various cancer cells 塞浦路斯蜜蜂(Apis mellifera cypria)毒液对各种癌细胞的细胞毒性和凋亡作用
Pub Date : 2024-04-11 DOI: 10.1515/tjb-2023-0109
Ayşe Nalbantsoy, Ekin Varol, Ayşe Dila Çaglar, B. Yücel
The bee stinger is the defense organ of honeybees. The venom sac of a worker bee is connected to its stinger, which is used as a defense mechanism, and it has a potent and complex combination of substances that is unique in the animal kingdom. Many immune-related illnesses have been successfully treated with bee venom and recent evidence on the efficacy of applications targeting malignancies has attracted considerable attention. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test was used to determine the cytotoxicity of the crude venom, and the flow cytometric analysis was used to determine the apoptotic potential. The cytotoxic activity of Apis mellifera cypria venom collected from two different apiaries in Cyprus was evaluated for the first time against breast (MDA-MB-231), colon (Caco-2), cervix (HeLa), prostate (PC-3), pancreas (Panc-1), lung (A549), glioblastoma (U-87MG) human cancerous and healthy lung fibroblast (CCD-34Lu) cells. The venom concentration that killed 50 % of the cells (inhibitory concentration, IC50) is expressed as venom cytotoxicity. The IC50 values of A. m. cypria crude venom on cultured cells varied from 4.18±0.75 to 22.00±1.71 μg/mL after treatment with crude venom for 48 h, with the most potent activities against PC-3, Panc-1, and HeLa cells. Analysis of apoptotic cells by flow cytometry of both venom samples showed that bee venom slightly induced early apoptosis on A549 and Panc-1 cells. The venom of the A. m. cypria is discussed in this article, displaying promising results as a potential source for an alternative treatment method because of its cytotoxic effect.
蜂刺是蜜蜂的防御器官。工蜂的毒囊与蜂刺相连,蜂刺是一种防御机制,它具有动物界独一无二的强效和复杂的物质组合。许多与免疫有关的疾病都成功地用蜂毒治疗过,最近关于针对恶性肿瘤的应用疗效的证据引起了人们的极大关注。 本研究采用 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-溴化四氮唑(MTT)试验测定粗蜂毒的细胞毒性,并采用流式细胞分析法测定细胞凋亡潜能。首次评估了从塞浦路斯两个不同养蜂场采集的蜜蜂毒液对乳腺(MDA-MB-231)、结肠(Caco-2)、宫颈(HeLa)、前列腺(PC-3)、胰腺(Panc-1)、肺(A549)、胶质母细胞瘤(U-87MG)人类癌细胞和健康肺成纤维细胞(CCD-34Lu)的细胞毒性活性。 杀死 50% 细胞的毒液浓度(抑制浓度,IC50)表示毒液的细胞毒性。用粗毒处理 48 小时后,A. m. cypria 粗毒对培养细胞的 IC50 值从 4.18±0.75 到 22.00±1.71 μg/mL 不等,其中对 PC-3、Panc-1 和 HeLa 细胞的活性最强。用流式细胞仪分析两种毒液样本的凋亡细胞显示,蜂毒可轻微诱导 A549 和 Panc-1 细胞早期凋亡。 本文讨论了A. m. cypria的毒液,由于其细胞毒性作用,它作为一种替代治疗方法的潜在来源显示出了良好的效果。
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引用次数: 0
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Turkish Journal of Biochemistry
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