Five candidate biomarkers associated with the diagnosis and prognosis of cervical cancer

Purpose: Cervical cancer (CC) is one of the most general gynecological malignancies and is associated with high morbidity and mortality. We aimed to select candidate genes related to the diagnosis and prognosis of CC.Methods: The mRNA expression profile datasets were downloaded. We also downloaded RNA-sequencing gene expression data and related clinical materials from TCGA, which included 307 CC samples and 3 normal samples. Differentially expressed genes (DEGs) were obtained by R software. GO function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed in the DAVID dataset. Using machine learning, the optimal diagnostic mRNA biomarkers for CC were identified. We used qRT-PCR and Human Protein Atlas (HPA) database to exhibit the differences in gene and protein levels of candidate genes.Results: A total of 313 DEGs were screened from the microarray expression profile datasets. DNA methyltransferase 1 (DNMT1), Chromatin Assembly Factor 1, subunit B (CHAF1B), Chromatin Assembly Factor 1, subunit A (CHAF1A), MCM2, CDKN2A were identified as optimal diagnostic mRNA biomarkers for CC. Additionally, the GEPIA database showed that the DNMT1, CHAF1B, CHAF1A, MCM2 and CDKN2A were associated with the poor survival of CC patients. HPA database and qRT-PCR confirmed that these genes were highly expressed in CC tissues.Conclusion: The present study identified five DEmRNAs, including DNMT1, CHAF1B, CHAF1A, MCM2 and Kinetochore-related protein 1 (KNTC1), as potential diagnostic and prognostic biomarkers of CC.     

Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach

Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers.     

Circulating antioxidant vitamins and copper in Azorean coronary artery disease patients under preventive medication – A case study

Background and aimOxidative stress and inflammation are conditions that are deeply involved in atherosclerosis and consequent coronary artery disease (CAD). Therefore, the aim of this study was to assess the relationship among circulating antioxidant vitamins (C, A, E), copper, and other pro- or antioxidant/inflammation markers in patients with and without CAD under preventive medication.Subjects and methods174 Azorean subjects symptomatic for CAD (age 56 ± 9y; 68 % men) submitted to coronary angiography were split into 2 groups: one formed by CAD patients (≥50 % stenosis in at least one major coronary vessel) and the other by non-CAD patients (<50 % stenosis). Both groups were age-, sex- and BMI-matched. Plasma levels of vitamins or copper were measured by HPLC and AAS, respectively.Results and conclusionsLower vitamin C levels were observed in CAD patients (mainly in women, who exhibited a high rate of diabetes mellitus) as compared to the non-CAD ones. Also, CAD patients (mainly men) exhibited significantly higher concentrations of plasma copper than their non-CAD counterparts (1.17 ± 0.3 mg/L vs. 1.09 ± 0.3 mg/L, p = 0.030). In bivariate analysis, plasma copper levels were positively associated with serum LDL-cholesterol (r=0.22; p = 0.004) and chiefly with C-reactive protein (r=0.40; p < 0.001). Furthermore, they were significantly lower in recurrent vs. non recurrent CAD patients (1.07±0.2 vs. 1.24±0.3 mg/L, p = 0.004). ROC analysis showed that plasma copper, whenever >1.06 mg/L, was an independent risk factor for CAD in primary prevention for men, which suggests that its levels can fluctuate with medical therapy (such as anti-inflammatory), thus indicating that copper is not a reliable marker for CAD. Moreover, plasma copper concentration was not associated with CAD severity. Yet, results do suggest that, even within its reference concentration range, it could be useful as an acute inflammation marker in CAD management.     

Dysregulation of metallothionein and zinc aggravates periodontal diseases

BackgroundPeriodontitis (PD) is a multifaceted inflammatory disease connected to bacterial infection that results in the destruction of tooth supporting structures and eventually tooth loss. Given their involvement in infection and inflammation, both metallothionein (MT) and zinc (Zn) might play vital roles in the development and progression of PD. More specifically, both MT and Zn are heavily involved in regulating immune functions, controlling bacterial infection, balancing inflammatory responses, and reducing oxidative stress, all of which are associated with the pathogenesis of PD.ObjectiveThis review paper will explore the physiological functions of MT and Zn and hypothesise how dysregulation could negatively affect periodontal health, leading to PD.FindingsBacterial lipopolysaccharide (LPS) derived from periodontal pathogens, namely P. gingivalis initiates the acute phase response, thus upregulating the expression of MT which leads to the subsequent deficiency of Zn, a hallmark of periodontal disease. This deficiency leads to ineffective NETosis, increases the permeability of the gingival epithelium, and disrupts the humoral immune response, collectively contributing to PD. In addition, the presence of LPS in Zn deficient conditions favours M1 macrophage polarisation and maturation of dendritic cells, and also inhibits the anti-inflammatory activity of regulatory T cells. Collectively, these observations could theoretically give rise to the chronic inflammation seen in PD.ConclusionA disrupted MT and Zn homeostasis is expected to exert an adverse impact on periodontal health and contribute to the development and progression of PD.     

高血压性心脏病生物标志物的筛选：基于中国重庆市7家医疗机构的数据分析研究*

目的: 筛选高血压性心脏病（HHD）的影响因素,建立HHD的预测模型,为HHD的发生提供预警。方法: 选取中国重庆市某医科院校数据研究院平台2016年1月1日至2019年12月31日主要诊断为高血压性心脏病和高血压患者。通过单因素分析、多因素分析筛选HHD的影响因素,采用R语言分别构建Logistics模型、随机森林（RF）模型和极限梯度上升（XGBoost）模型。结果: 单因素分析筛选出60项差异指标,多因素分析筛选出18项差异指标（P<0.05）。Logistics模型、RF模型、XGBoost模型曲线下面积（AUC）分别为0.979、0.983和0.990。结论: 本文建立的3种HHD预测模型结果稳定,其中XGBoost模型对于HHD的发生具有良好的诊断效应。     

柚皮苷通过P2X7受体减轻HIV-1包膜糖蛋白gp120导致大鼠神经功能损害的的作用及机制

人类免疫缺陷病毒-1(Human immunodeficiency virus-1,HIV-1)包膜糖蛋白gp120能够引起大鼠出现学习记忆障碍的行为学改变并增加海马中P2X7受体的表达;柚皮苷对gp120引起的行为学改变及P2X7表达增多具有改善作用。为了研究柚皮苷通过减少P2X7受体表达减轻gp120导致大鼠神经功能损害的作用及机制,本实验选择SD大鼠并分为假手术操作的对照组、脑室注射gp120的gp120组、脑室注射gp120及不同剂量柚皮苷灌胃的柚皮苷组、脑室注射BzATP的BzATP组、脑室注射gp120、BzATP及90mg/kg柚皮苷灌胃的90mg/kg/d柚皮苷+BzATP组。Morris水迷宫检测逃避潜伏期及错误次数,TUNEL法检测海马中细胞凋亡率,Elisa法检测海马中肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白介素-1β(Interleukin-1β,IL-1β)、白介素-6(Interleukin-6,IL-6)的含量,Western blot检测海马中P2X7受体的表达。结果显示:与对照组比较,gp120组大鼠的逃避潜伏期延长,错误次数及海马中细胞凋亡率、TNF-α、IL-1β、IL-6的含量、P2X7受体的表达水平增加(P<0.05);与gp120组比较,不同剂量柚皮苷组大鼠的逃避潜伏期缩短,错误次数及海马中细胞凋亡率、TNF-α、IL-1β、IL-6的含量、P2X7受体的表达水平减少(P<0.05);与90mg/kg/d柚皮苷组比较,90mg/kg/d柚皮苷+BzATP组大鼠的逃避潜伏期延长,错误次数及海马中细胞凋亡率、TNF-α、IL-1β、IL-6的含量、P2X7受体的表达水平增加(P<0.05)。本研究的结果表明柚皮苷减轻HIV-1包膜糖蛋白gp120诱导的神经功能损害,这一作用与抑制海马组织中P2X7受体表达并减轻炎症反应及细胞凋亡有关。创新在于首次阐明了柚皮苷减轻HIV-1包膜糖蛋白gp120诱导神经功能损害的分子机制。在gp120引起大鼠行为学改变及海马组织中细胞凋亡、炎症反应激活的过程中,柚皮苷通过抑制P2X7受体的表达来改善行为学改变、抑制细胞凋亡及炎症反应的激活。     

熊去氧胆酸对阿霉素诱导的H9c2心肌细胞的影响及机制研究

目的:探讨熊去氧胆酸(UDCA)对阿霉素(DOX)诱导的H9c2心肌细胞损伤的影响及机制。方法:体外培养H9c2细胞,1μM DOX和不同浓度UDCA处理H9c2,CCK-8法测定细胞活力;实时定量聚合酶链反应检测心肌细胞凋亡分子Bax及炎症因子IL-1β、IL-6的表达;Western blotting检测UDCA对DOX诱导的心肌细胞凋亡相关蛋白Bax、Bcl2、Caspase3表达水平变化。结果:与对照组相比,DOX组心肌细胞活力减弱;炎症因子IL-1β,IL-6表达上调;促凋亡分子Bax和cleaved Caspase3表达增多;抑制凋亡蛋白Bcl2下调(P<0.05)。与DOX组相比,UDCA+DOX组显著恢复心肌细胞活力;炎症因子IL-1β、IL-6表达下调;促凋亡分子Bax、cleaved Caspase3下调;抑制凋亡蛋白Bcl2表达上调(P<0.05)。结论:UDCA能缓解DOX诱导的H9c2心肌细胞损伤,其机制可能与抑制炎症及凋亡有关。本研究为阿霉素心肌毒性的防治提供新的实验基础及理论依据。     

尿液诊断膀胱癌的研究进展

摘要：膀胱癌是临床常见的发生在泌尿系统的恶性肿瘤,该病的发病率呈现逐年升高的趋势,其复发率也相对较高。早期诊断和定期随访是保证膀胱癌患者长期生存的关键。对于膀胱癌的诊断以及患者的随访通常凭借膀胱镜检查或尿脱落细胞学的测定。然而,前者的检查费用较为昂贵,且属于有创诊断;后者则具有检查敏感性相对较低的特点,还存在较大程度受病理科诊断医生主观因素影响的局限,目前还没有尿液生物标志物可以替代传统的诊断方法。膀胱肿瘤具有广泛的异质性,不同的疾病表型具有不同的分子差异。因此,引入尿液生物标志物来诊断疾病,评估疾病的侵袭性、进展的风险、复发的可能性和预后具有重要的临床价值。本文总结了目前尿液所含生物标志物诊断膀胱癌的研究现状,并对此领域的主要研究进展进行综述。