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Genetic Association Between Polycystic Ovary Syndrome and the APOA5 rs662799 and PLIN1 rs894160 Metabolic Variants in the Western Saudi Population: A Case-Control Study. 沙特西部人群中多囊卵巢综合征与 APOA5 rs662799 和 PLIN1 rs894160 代谢变异之间的遗传关联:一项病例对照研究。
IF 3.8 Q2 Medicine Pub Date : 2024-06-16 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241258585
Sherin Bakhashab, Asma A Batarfi, Mahinar M Alhartani, Rola Turki, Wessam Mady

Background: Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS pathogenesis is complex and multifactorial, involving genetic and environmental factors.

Objectives: This study aimed to determine and compare genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (APOA5; rs662799) and perilipin 1 (PLIN1; rs894160, rs1052700 and rs6496589) genes in Western Saudi women to investigate their association with PCOS and its clinical characteristics.

Design and methods: This was a case-control study conducted on women with (n = 104) and without (n = 87) PCOS. The SNPs were genotyped using TaqMan genotyping assays.

Results: Significant and direct associations were detected between PCOS susceptibility and APOA5 SNP rs662799 and PLIN1 SNP rs894160 (P < .001). For APOA5 SNP rs662799, women with the A allele were more likely to have PCOS (relative risk [RR] = 1.348, odds ratio [OR] = 2.313, P < .001) and hypertriglyceridaemia (OR = 17.0, P = .5) than women with the G allele. For PLIN1 SNP rs894160, women with the T allele were more likely to have PCOS than women with the C allele (RR = 8.043, OR = 7.427, P < .001). For PLIN1 SNP rs1052700, women with the TT genotype were more likely to have hyperandrogenism (OR = 29.75, P = .02) and an irregular period (OR = 0.07, P = .040) than women with the AT genotype.

Conclusion: We identified novel alleles and genotypes contributing to the genetic risk of PCOS in the Western Saudi population.

背景:多囊卵巢综合征(PCOS)是影响育龄妇女的一种常见内分泌疾病,与胰岛素抵抗和肥胖有关。多囊卵巢综合征的发病机制复杂且多因素,涉及遗传和环境因素:本研究旨在确定和比较西方沙特妇女中载脂蛋白 A5(APOA5;rs662799)和周脂素 1(PLIN1;rs894160、rs1052700 和 rs6496589)基因中单核苷酸多态性(SNPs)的基因型和等位基因频率,以调查它们与多囊卵巢综合征及其临床特征的关系:这是一项病例对照研究,研究对象为患有多囊卵巢综合征(104 人)和未患有多囊卵巢综合征(87 人)的妇女。采用 TaqMan 基因分型测定法对 SNPs 进行基因分型:结果:PCOS 易感性与 APOA5 SNP rs662799 和 PLIN1 SNP rs894160 之间存在显著的直接关联(P APOA5 SNP rs662799,等位基因为 A 的女性比等位基因为 G 的女性更容易患 PCOS(相对风险 [RR] = 1.348,几率比 [OR] = 2.313,P P = .5)。就 PLIN1 SNP rs894160 而言,T 等位基因女性比 C 等位基因女性更有可能患有多囊卵巢综合征(RR = 8.043,OR = 7.427,P PLIN1 SNP rs1052700,TT 基因型女性比 AT 基因型女性更有可能患有高雄激素症(OR = 29.75,P = .02)和月经不调(OR = 0.07,P = .040):结论:我们在沙特西部人群中发现了导致多囊卵巢综合症遗传风险的新等位基因和基因型。
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引用次数: 0
Novel Serum Proteomes Expressed from Benzene Exposure Among Gasoline Station Attendants. 加油站服务员因接触苯而表达的新血清蛋白质组
IF 3.8 Q2 Medicine Pub Date : 2024-06-10 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241259604
Chan Pattama Polyong, Sittiruk Roytrakul, Jintana Sirivarasai, Tanongsak Yingratanasuk, Anamai Thetkathuek

Background: Research on the proteomes impact of benzene exposure in fuel station employees remains sparse, underscoring the need for detailed health impact assessments focusing on biomarker evaluation.

Objectives: This investigation aimed to analyze the differences in blood parameters and serum proteomes resulting from benzene exposure between gasoline station attendants (B-GSA) and a control group.

Design and methods: A cross-sectional analytical study was conducted with 96 participants, comprising 54 in the B-GSA group and 42 in the control group. The methodology employed included an interview questionnaire alongside urine and blood sample collections. The urine samples were analyzed for trans,trans-muconic acid (t,t-MA) levels, while the blood samples underwent complete blood count analysis and proteome profiling.

Results: Post-shift analysis indicated that the B-GSA group exhibited significantly higher levels of t,t-MA and monocytes compared to the control group (P < .05). Proteome quantification identified 1448 proteins differentially expressed between the B-GSA and control groups. Among these, 20 proteins correlated with the levels of t,t-MA in urine. Notably, 4 proteins demonstrated more than a 2-fold down-regulation in the B-GSA group: HBS1-like, non-structural maintenance of chromosomes element 1 homolog, proprotein convertase subtilisin/kexin type 4, and zinc finger protein 658. The KEGG pathway analysis revealed associations with apoptosis, cancer pathways, p53 signaling, and the TNF signaling pathway.

Conclusion: The changes in these 4 significant proteins may elucidate the molecular mechanisms underlying benzene toxicity and suggest their potential as biomarkers for benzene poisoning in future assessments.

背景:有关苯暴露对加油站员工的蛋白质组影响的研究仍然很少,这突出表明需要以生物标志物评估为重点进行详细的健康影响评估:本调查旨在分析加油站员工(B-GSA)与对照组之间因接触苯而导致的血液参数和血清蛋白质组的差异:对 96 名参与者进行了横断面分析研究,其中 54 人属于 B-GSA 组,42 人属于对照组。采用的方法包括采访问卷以及尿样和血样采集。对尿样进行了反式、反式粘多酸(t,t-MA)水平分析,对血样进行了全血细胞计数分析和蛋白质组分析:转移后分析表明,与对照组相比,B-GSA 组的 t,t-MA和单核细胞水平明显更高(尿液中的 t,t-MA,P<0.05)。值得注意的是,有 4 种蛋白质在 B-GSA 组中的下调幅度超过 2 倍:HBS1-like、染色体非结构维持元件 1 同源物、4 型枯草蛋白/kexin 丙蛋白转换酶和 658 锌指蛋白。KEGG 通路分析显示,这些蛋白与细胞凋亡、癌症通路、p53 信号转导和 TNF 信号转导通路有关:结论:这 4 种重要蛋白质的变化可能会阐明苯中毒的分子机制,并表明它们在未来的评估中可能成为苯中毒的生物标志物。
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引用次数: 0
MicroRNAs in Umbilical Cord Blood and Development in Full-Term Newborns: A Prospective Study. 脐带血中的 MicroRNA 与足月新生儿的发育:一项前瞻性研究
IF 3.8 Q2 Medicine Pub Date : 2024-06-10 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241258017
Liang-Jen Wang, Ching-Chang Tsai, How-Ran Chao, Sheng-Yu Lee, Chih-Cheng Chen, Sung-Chou Li

Background: Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays.

Objectives: Hence, this research seeks to investigate if the expression of miRNA in the umbilical cord blood of infants can forecast their developmental outcomes as they grow older.

Design and method: We enrolled 143 full-term newborns, delivered either via cesarean section (CS) or through natural spontaneous delivery (NSD). We then analyzed the profiles of specific miRNAs (miR-486-5p, miR-126-5p, miR-140-3p, miR-151a-3p, miR-142-5p, and miR-30e-5p) in the umbilical cord blood of these infants. Subsequently, we performed follow-up assessments using Bayley-III scores when the cohort reached 1 year of age. Furthermore, we conducted pathway-enrichment analyses on the target genes associated with these examined miRNAs.

Results: When comparing newborns delivered via cesarean section (CS) to those born via natural spontaneous delivery (NSD), we observed notable differences. Specifically, newborns through NSD displayed significantly higher ΔCt values for miR-486-5p, alongside lower ΔCt values for miR-126-5p and miR-151a-3p in their cord blood. At 1 year of age, cognitive development was significantly linked to the ΔCt values of miR-140-3p and miR-142-5p, while language development showed a significant association with the ΔCt values of miR-140-3p. Moreover, our pathway enrichment analyses revealed that the target genes of these miRNAs were consistently involved in the pathways related to neurons, such as axon guidance and the neurotrophin signaling pathway.

Conclusion: In summary, this study represents a pioneering effort in elucidating the potential connections between miRNA levels in cord blood and the health indicators and neurodevelopment of newborns at 1 year of age. Our findings underscore the significance of miRNA levels at birth in influencing mechanisms related to neurodevelopment.

背景:探索新生儿的表观遗传调控(如microRNA)对提高我们应对和潜在预防生命早期发育迟缓的能力具有重大意义:因此,本研究试图探讨婴儿脐带血中 miRNA 的表达能否预测他们长大后的发育结果:我们招募了 143 名足月产新生儿,他们均通过剖腹产(CS)或自然顺产(NSD)分娩。然后,我们分析了这些婴儿脐带血中特定 miRNA(miR-486-5p、miR-126-5p、miR-140-3p、miR-151a-3p、miR-142-5p 和 miR-30e-5p)的特征。随后,我们使用 Bayley-III 评分对这些满 1 岁的婴儿进行了随访评估。此外,我们还对与这些受检 miRNA 相关的靶基因进行了通路富集分析:结果:在比较剖腹产(CS)新生儿和自然顺产(NSD)新生儿时,我们观察到了明显的差异。具体来说,NSD新生儿的脐带血中miR-486-5p的ΔCt值明显较高,而miR-126-5p和miR-151a-3p的ΔCt值较低。1岁时,认知发展与miR-140-3p和miR-142-5p的ΔCt值显著相关,而语言发展则与miR-140-3p的ΔCt值显著相关。此外,我们的通路富集分析表明,这些 miRNA 的靶基因始终参与与神经元相关的通路,如轴突导向和神经营养素信号通路:总之,这项研究开创性地阐明了脐带血中 miRNA 水平与新生儿 1 岁时的健康指标和神经发育之间的潜在联系。我们的研究结果强调了出生时 miRNA 水平对神经发育相关机制的重要影响。
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引用次数: 0
Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression. PLA2R1 和 HLA DQA1 基因的 10 个多态性与原发性膜性肾病风险的关系:一项 Meta 分析和一项 Meta 回归。
IF 3.8 Q2 Medicine Pub Date : 2024-06-10 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241259602
Tarak Dhaouadi, Awatef Riahi, Taïeb Ben Abdallah, Yousr Gorgi, Imen Sfar

Background: Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies heterogeneity needs to be investigated.

Objectives: The aim of this review was to summarize existing data on the contribution of 10 SNPs in the PLA2R and HLA-DQA1 genes to PMN susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions.

Design: This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses.

Data sources and methods: An electronic literature search for eligible studies among all papers published prior to January 10, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the 10 following SNPs: rs4664308, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, rs2715918, and rs2187668.

Results: Combined analyses revealed a significant increase in PMN risk conferred by the following alleles: rs4664308*A, rs3749117*T, rs3749119*C, rs35771982*G, rs3828323*C, rs16844715*C, rs1511223*A, rs2715918*A, and rs2187668*A, all P-values < .001. Moreover, the PLA2R-rs4664308/HLA-DQA1-rs2187668 interaction was significantly associated with an increased PMN risk, P < .001. However, there was a substantial between-studies heterogeneity for some SNPs. Subgroup analyses by ethnicity for the 9 PLA2R SNPs did not show any cross-ethnic disparity. Inversely, the risk conferred by the HLA-DQA1 rs2187668*A allele was significantly higher in Caucasians (OR [95% CI] = 3.929 [3.251-4.748]) than in Asians (OR [95% CI] = 2.537 [1.94-3.318], P = .007. Besides, meta-regressions revealed for the majority of investigated SNPs significant correlations of the effect size with albumin, 24-hours proteinuria, serum creatinine, and eGFR levels. Hence, the influence on PMN risk conferred by the PLA2R and HLA-DQA1 SNPs was rather noted in patients with a severe disease.

Conclusion: This meta-analysis showed that 9 out of the 10 investigated SNPs in PLA2R and HLA-DQA1 genes were associated with increased PMN risk. Heterogeneity could be due to disparate patient groups in terms of disease presentation for almost all SNPs, and ethnicity for the HLA-DQA1 rs2187668 SNP.

Registration: This review has been registered on PROSPERO: CRD42024506729. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729.

背景:尽管已有多项研究评估了磷脂酶A2受体(PLA2R)和HLA-DQA1 SNPs与原发性膜性肾病(PMN)的相关性,但结果并不一致,而且需要调查研究间的异质性:本综述旨在总结 PLA2R 和 HLA-DQA1 基因中 10 个 SNPs 对原发性膜性肾病易感性影响的现有数据,并通过亚组分析和元回归研究不同研究之间的异质性:本研究根据系统综述和荟萃分析的PRISMA指南进行:通过PubMed、EMBASE、Web of science和Scopus数据库对2024年1月10日之前发表的所有论文中符合条件的研究进行了电子文献检索。针对以下 10 个 SNPs 进行了元分析、亚组分析和元回归:rs4664308、rs3749117、rs3749119、rs35771982、rs3828323、rs16844715、rs1511223、rs6757188、rs2715918 和 rs2187668:综合分析显示,以下等位基因会显著增加 PMN 风险:rs4664308*A、rs3749117*T、rs3749119*C、rs35771982*G、rs3828323*C、rs16844715*C、rs1511223*A、rs2715918*A 和 rs2187668*A,所有 P 值均为 P = .007。此外,元回归显示,大多数被研究的 SNPs 的效应大小与白蛋白、24 小时蛋白尿、血清肌酐和 eGFR 水平有显著相关性。因此,PLA2R 和 HLA-DQA1 SNPs 对 PMN 风险的影响在重症患者中更为明显:这项荟萃分析表明,PLA2R 和 HLA-DQA1 基因的 10 个 SNPs 中,有 9 个与 PMN 风险增加有关。异质性可能是由于几乎所有SNPs的疾病表现和HLA-DQA1 rs2187668 SNP的种族不同造成的:本综述已在 PROSPERO 上注册:CRD42024506729。可从以下网址获取:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729。
{"title":"Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression.","authors":"Tarak Dhaouadi, Awatef Riahi, Taïeb Ben Abdallah, Yousr Gorgi, Imen Sfar","doi":"10.1177/11772719241259602","DOIUrl":"10.1177/11772719241259602","url":null,"abstract":"<p><strong>Background: </strong>Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies heterogeneity needs to be investigated.</p><p><strong>Objectives: </strong>The aim of this review was to summarize existing data on the contribution of 10 SNPs in the PLA2R and HLA-DQA1 genes to PMN susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions.</p><p><strong>Design: </strong>This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses.</p><p><strong>Data sources and methods: </strong>An electronic literature search for eligible studies among all papers published prior to January 10, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the 10 following SNPs: rs4664308, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, rs2715918, and rs2187668.</p><p><strong>Results: </strong>Combined analyses revealed a significant increase in PMN risk conferred by the following alleles: rs4664308*A, rs3749117*T, rs3749119*C, rs35771982*G, rs3828323*C, rs16844715*C, rs1511223*A, rs2715918*A, and rs2187668*A, all <i>P</i>-values < .001. Moreover, the PLA2R-rs4664308/HLA-DQA1-rs2187668 interaction was significantly associated with an increased PMN risk, <i>P</i> < .001. However, there was a substantial between-studies heterogeneity for some SNPs. Subgroup analyses by ethnicity for the 9 PLA2R SNPs did not show any cross-ethnic disparity. Inversely, the risk conferred by the HLA-DQA1 rs2187668*A allele was significantly higher in Caucasians (OR [95% CI] = 3.929 [3.251-4.748]) than in Asians (OR [95% CI] = 2.537 [1.94-3.318], <i>P</i> = .007. Besides, meta-regressions revealed for the majority of investigated SNPs significant correlations of the effect size with albumin, 24-hours proteinuria, serum creatinine, and eGFR levels. Hence, the influence on PMN risk conferred by the PLA2R and HLA-DQA1 SNPs was rather noted in patients with a severe disease.</p><p><strong>Conclusion: </strong>This meta-analysis showed that 9 out of the 10 investigated SNPs in PLA2R and HLA-DQA1 genes were associated with increased PMN risk. Heterogeneity could be due to disparate patient groups in terms of disease presentation for almost all SNPs, and ethnicity for the HLA-DQA1 rs2187668 SNP.</p><p><strong>Registration: </strong>This review has been registered on PROSPERO: CRD42024506729. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of Cytokeratin-18, C-peptide, MHR, and MACK-3 Biomarkers in Metabolic Dysfunction-Associated Fatty Liver Disease After Laparoscopic Sleeve Gastrectomy. 腹腔镜袖状胃切除术后代谢功能障碍相关脂肪肝中细胞角蛋白-18、C-肽、MHR 和 MACK-3 生物标志物的影响
IF 3.8 Q2 Medicine Pub Date : 2024-06-03 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241256496
Mohamed Hany, Hala M Demerdash, Anwar Ashraf Abouelnasr, Bart Torensma

Background: Laparoscopic sleeve gastrectomy (LSG) has emerged as a valuable treatment for various metabolic disorders, including metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with obesity. Consequently, there is a pressing need to develop noninvasive biomarkers for diagnosing and monitoring disease progression.

Objectives: This study aimed to evaluate specific biomarkers, including Cytokeratin-18 (CK-18), C-peptide, monocyte to HDL cholesterol ratio (MHR), and MACK-3, in patients with obesity with MAFLD undergoing LSG.

Design: A prospective cohort study on patients with obesity before and 6 months after the LSG procedure.

Methods: 70 patients with obesity with confirmed MAFLD, determined by Transient Elastography (TE), were pre- and 6 months postoperatively tested. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), lipid profile, ghrelin, leptin, peptide YY, GLP-1, and liver fibrosis scores, including AST/ALT ratio (AAR), Fibrosis-4 index (FIB-4), and BARD Score were tested.

Results: BMI significantly decreased in all participants, with a % excess weight loss of 62.0% ± 15.4%. TE measurements revealed a significant postoperative reduction from 100% to 87.1% (P = .006). All selected biomarkers showed significant postoperative improvement-a significant association of CK-18 with MAFLD markers, including AAR, FIB-4, and BARD score, were found. MACK-3 had positive associations with FIB-4. C-peptide and MHR showed no association with MAFLD markers. Furthermore, there was a positive correlation between CK-18 and MACK-3 tests and between C-peptide and CK-18 and MACK-3. Additionally, a receiver operating characteristic (ROC) curve was constructed, with CK-18 performing the best, with an estimated area under the curve of 0.863.

Conclusion: Serum CK-18 outperformed other selected biomarkers in predicting and monitoring MAFLD in patients with obesity, suggesting its prospective utility in clinical practice. Further studies are needed to validate the accuracy of the MACK-3 test.

背景:腹腔镜袖带胃切除术(LSG)已成为治疗各种代谢性疾病,包括肥胖症患者代谢功能障碍相关性脂肪肝(MAFLD)的重要方法。因此,迫切需要开发用于诊断和监测疾病进展的无创生物标志物:本研究旨在评估接受 LSG 治疗的肥胖症 MAFLD 患者的特定生物标志物,包括细胞角蛋白-18 (CK-18)、C 肽、单核细胞与高密度脂蛋白胆固醇比值 (MHR) 和 MACK-3:方法:对 70 名经瞬态弹性成像(TE)确定患有 MAFLD 的肥胖患者进行术前和术后 6 个月的检测。测试内容包括胰岛素抵抗静态模型评估(HOMA-IR)、血脂谱、胃泌素、瘦素、YY 肽、GLP-1 和肝纤维化评分,包括 AST/ALT 比值(AAR)、纤维化-4 指数(FIB-4)和 BARD 评分:结果:所有参与者的体重指数均明显下降,超重率为 62.0% ± 15.4%。TE测量结果显示,术后体重从100%降至87.1%(P = .006)。所有选定的生物标志物在术后都有明显改善--CK-18 与 MAFLD 标志物(包括 AAR、FIB-4 和 BARD 评分)有显著关联。MACK-3与FIB-4呈正相关。C肽和MHR与MAFLD指标没有关联。此外,CK-18 和 MACK-3 检测之间以及 C 肽与 CK-18 和 MACK-3 之间存在正相关。此外,还构建了接收器操作特征曲线(ROC),其中 CK-18 的表现最佳,估计曲线下面积为 0.863:结论:在预测和监测肥胖症患者的 MAFLD 方面,血清 CK-18 优于其他选定的生物标志物,这表明它在临床实践中具有前瞻性的作用。还需要进一步的研究来验证 MACK-3 检测的准确性。
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引用次数: 0
Are We Using Ezetimibe As Much As We Should? 依折麦布的使用量是否达到了我们应该使用的程度?
IF 3.8 Q2 Medicine Pub Date : 2024-05-31 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241257410
Antonis A Manolis, Theodora A Manolis, Dimitri P Mikhailidis, Antonis S Manolis

Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance.

降脂疗法,尤其是非他汀类药物治疗方案,一直未得到充分利用,因为约有 2/3 的动脉粥样硬化性心血管疾病(CVD)患者未得到最佳治疗,尽管接受了他汀类药物治疗,但低密度脂蛋白胆固醇(LDL-C)浓度仍未达到目标水平。他汀类药物一直是降血脂疗法的主流,但其不良反应较多,这在一定程度上阻碍了他汀类药物的广泛应用。依折麦布通常是实现低密度脂蛋白胆固醇目标的首选治疗方式,因为它不仅疗效好,而且可以使用较小剂量的他汀类药物,同时还无需使用更昂贵的疗法。我们在此对依折麦布在降脂、减少心血管事件和改善预后方面的效果进行了全面回顾。在降脂疗法中,口服依折麦布与新型药物相比,是最方便和/或最经济实惠的方案,可作为单一或联合疗法使用,CV 结果研究的数据证明了其在降低 CVD 风险和事件方面的疗效。当与他汀类药物联合使用时,他汀类药物的剂量可以降低,从而减少副作用,同时降脂效果也会增强(约20%),因为达到目标水平LDL-C的患者比例(
{"title":"Are We Using Ezetimibe As Much As We Should?","authors":"Antonis A Manolis, Theodora A Manolis, Dimitri P Mikhailidis, Antonis S Manolis","doi":"10.1177/11772719241257410","DOIUrl":"10.1177/11772719241257410","url":null,"abstract":"<p><p>Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers. 用于泌尿生殖系统癌症免疫检查点阻断的生物标志物不断发展。
IF 3.8 Q2 Medicine Pub Date : 2024-05-31 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241254179
Seema Mustafa, Caroline S Jansen, Yash Jani, Sean Evans, Tony Z Zhuang, Jacqueline Brown, Bassel Nazha, Viraj Master, Mehmet Asim Bilen

In the past decade, immune checkpoint inhibitors (ICI) have been approved for treatment of genitourinary malignancies and have revolutionized the treatment landscape of these tumors. However, despite the remarkable success of these therapies in some GU malignancies, many patients' tumors do not respond to these therapies, and others may experience significant side effects, such as immune-related adverse events (iRAEs). Accordingly, biomarkers and improved prognostic tools are critically needed to help predict which patients will respond to ICI, predict and mitigate risk of developing immune-related adverse events, and inform personalized choice of therapy for each patient. Ongoing clinical and preclinical studies continue to provide an increasingly robust understanding of the mechanisms of the response to immunotherapy, which continue to inform biomarker development and validation. Herein, we provide a comprehensive review of biomarkers of the response to immunotherapy in GU tumors and their role in selection of therapy and disease monitoring.

在过去十年中,免疫检查点抑制剂(ICI)已被批准用于治疗泌尿生殖系统恶性肿瘤,并彻底改变了这些肿瘤的治疗格局。然而,尽管这些疗法在一些泌尿生殖系统恶性肿瘤中取得了显著的成功,但许多患者的肿瘤对这些疗法没有反应,还有一些患者可能会出现严重的副作用,如免疫相关不良事件(iRAEs)。因此,亟需生物标志物和改进的预后工具来帮助预测哪些患者会对 ICI 产生反应,预测并降低发生免疫相关不良事件的风险,并为每位患者选择个性化疗法提供信息。正在进行的临床和临床前研究不断加深了人们对免疫疗法反应机制的理解,为生物标志物的开发和验证提供了依据。在此,我们将全面综述GU肿瘤免疫疗法反应的生物标志物及其在疗法选择和疾病监测中的作用。
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引用次数: 0
Comparative Analysis of Biomarkers in Type 2 Diabetes Patients With and Without Comorbidities: Insights Into the Role of Hypertension and Cardiovascular Disease. 有合并症和无合并症的 2 型糖尿病患者的生物标志物比较分析:洞察高血压和心血管疾病的作用。
IF 3.8 Q2 Medicine Pub Date : 2024-05-04 eCollection Date: 2024-01-01 DOI: 10.1177/11772719231222111
Symeon Savvopoulos, Haralampos Hatzikirou, Herbert F Jelinek

Background: Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by biochemical and physical characteristics including glycemia, glycated hemoglobin (HbA1c), and tests for cardiovascular, eye and kidney disease.

Objectives: Diabetes may have a common etiology based on inflammation and oxidative stress that may provide additional information about disease progression and treatment options. Thus, identifying high-risk individuals can delay or prevent diabetes and its complications.

Design: In patients with or without hypertension and cardiovascular disease, as part of progression from no diabetes to T2DM, this research studied the changes in biomarkers between control and prediabetes, prediabetes to T2DM, and control to T2DM, and classified patients based on first-attendance data. Control patients and patients with hypertension, cardiovascular, and with both hypertension and cardiovascular diseases are 156, 148, 61, and 216, respectively.

Methods: Linear discriminant analysis is used for classification method and feature importance, This study examined the relationship between Humanin and mitochondrial protein (MOTSc), mitochondrial peptides associated with oxidative stress, diabetes progression, and associated complications.

Results: MOTSc, reduced glutathione and glutathione disulfide ratio (GSH/GSSG), interleukin-1β (IL-1β), and 8-isoprostane were significant (P < .05) for the transition from prediabetes to t2dm, highlighting importance of mitochondrial involvement. complement component 5a (c5a) is a biomarker associated with disease progression and comorbidities, gsh gssg, monocyte chemoattractant protein-1 (mcp-1), 8-isoprostane being most important biomarkers.

Conclusions: Comorbidities affect the hypothesized biomarkers as diabetes progresses. Mitochondrial oxidative stress indicators, coagulation, and inflammatory markers help assess diabetes disease development and provide appropriate medications. Future studies will examine longitudinal biomarker evolution.

背景:2 型糖尿病(T2DM)占糖尿病病例的 90%,其患病率和发病率(包括合并症)在全球范围内呈上升趋势。临床上,糖尿病和相关合并症可通过生化和物理特征(包括血糖、糖化血红蛋白(HbA1c)以及心血管、眼部和肾脏疾病检测)来识别:糖尿病可能具有基于炎症和氧化应激的共同病因,这可能提供有关疾病进展和治疗方案的更多信息。因此,识别高危人群可以延缓或预防糖尿病及其并发症:设计:在患有或不患有高血压和心血管疾病的患者中,作为从无糖尿病到 T2DM 进展的一部分,本研究调查了糖尿病控制期与糖尿病前期、糖尿病前期与 T2DM、糖尿病控制期与 T2DM 之间生物标志物的变化,并根据首次就诊数据对患者进行了分类。对照组患者和高血压、心血管以及同时患有高血压和心血管疾病的患者分别为 156 人、148 人、61 人和 216 人:本研究考察了人血清素与线粒体蛋白(MOTSc)、与氧化应激相关的线粒体肽、糖尿病进展及相关并发症之间的关系:结果:MOTSc、还原型谷胱甘肽和谷胱甘肽二硫化物比率(GSH/GSSG)、白细胞介素-1β(IL-1β)和8-异前列腺素均有显著性差异(P随着糖尿病的发展,合并症会影响假设的生物标志物。线粒体氧化应激指标、凝血和炎症标志物有助于评估糖尿病疾病的发展并提供适当的药物。未来的研究将考察生物标志物的纵向演变。
{"title":"Comparative Analysis of Biomarkers in Type 2 Diabetes Patients With and Without Comorbidities: Insights Into the Role of Hypertension and Cardiovascular Disease.","authors":"Symeon Savvopoulos, Haralampos Hatzikirou, Herbert F Jelinek","doi":"10.1177/11772719231222111","DOIUrl":"https://doi.org/10.1177/11772719231222111","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by biochemical and physical characteristics including glycemia, glycated hemoglobin (HbA1c), and tests for cardiovascular, eye and kidney disease.</p><p><strong>Objectives: </strong>Diabetes may have a common etiology based on inflammation and oxidative stress that may provide additional information about disease progression and treatment options. Thus, identifying high-risk individuals can delay or prevent diabetes and its complications.</p><p><strong>Design: </strong>In patients with or without hypertension and cardiovascular disease, as part of progression from no diabetes to T2DM, this research studied the changes in biomarkers between control and prediabetes, prediabetes to T2DM, and control to T2DM, and classified patients based on first-attendance data. Control patients and patients with hypertension, cardiovascular, and with both hypertension and cardiovascular diseases are 156, 148, 61, and 216, respectively.</p><p><strong>Methods: </strong>Linear discriminant analysis is used for classification method and feature importance, This study examined the relationship between Humanin and mitochondrial protein (MOTSc), mitochondrial peptides associated with oxidative stress, diabetes progression, and associated complications.</p><p><strong>Results: </strong>MOTSc, reduced glutathione and glutathione disulfide ratio (GSH/GSSG), interleukin-1β (IL-1β), and 8-isoprostane were significant (<i>P</i> < .05) for the transition from prediabetes to t2dm, highlighting importance of mitochondrial involvement. complement component 5a (c5a) is a biomarker associated with disease progression and comorbidities, gsh gssg, monocyte chemoattractant protein-1 (mcp-1), 8-isoprostane being most important biomarkers.</p><p><strong>Conclusions: </strong>Comorbidities affect the hypothesized biomarkers as diabetes progresses. Mitochondrial oxidative stress indicators, coagulation, and inflammatory markers help assess diabetes disease development and provide appropriate medications. Future studies will examine longitudinal biomarker evolution.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11069335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating the Role of Methylated Circulating Tumor DNA in Combination With Pathological Prognostic Factors for Predicting Recurrence of Colorectal Cancer. 评估甲基化循环肿瘤 DNA 与病理预后因素相结合在预测结直肠癌复发方面的作用
IF 3.8 Q2 Medicine Pub Date : 2024-02-28 eCollection Date: 2024-01-01 DOI: 10.1177/11772719241232870
Hiba Al Naji, Jean M Winter, Susanne K Pedersen, Amitesh Roy, Susan E Byrne, Graeme P Young, Erin L Symonds

Background: Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor DNA (ctDNA) at diagnosis could be used to improve the prediction for disease recurrence.

Objectives: To assess the impact of detecting methylated BCAT1/IKZF1 ctDNA at diagnosis in combination with demographic, lifestyle, clinical factors and tumor pathology, to assess predictive value for recurrence.

Design: A retrospective cohort study.

Methods: The cohort included 180 patients (36 with recurrent CRC), who had undergone complete treatment and surveillance for a minimum of 3 years. Participant clinical details and ctDNA methylated BCAT1/IKZF1 results were compared between those with and without recurrence, and cox regression analysis assessed each factor on disease-free survival.

Results: Clinical factors independently associated with reduced disease-free survival included nodal involvement (HR = 3.83, 95% CI 1.56-9.43, P = .003), M1 stage (HR = 4.41, 95% CI 1.18-16.45, P = .027), a resection margin less than 2 mm (HR = 4.60, 95% CI 1.19-17.76, P = .027), perineural involvement (HR = 2.50, 95% CI 1.01-6.17, P = .047) and distal tumors (HR = 3.13, 95% CI 1.07-9.18, P = .037). Methylated BCAT1/IKZF1 was detected in 51.7% (93/180) of pre-treatment plasma samples. When a positive ctDNA finding was considered in combination with these clinical prognostic factors, there was improved predictive power of recurrence for patients with perineural involvement (HR = 4.44, 95% CI 1.92-10.26, P < .001), and it marginally improved the predictive factor for M1 stage (HR = 7.59, 95% CI 2.30-25.07, P = .001) and distal tumors (HR = 5.04, 95% CI 1.88-13.49, P = .001).

Conclusions: Nodal invasion, metastatic disease, distal tumor site, low resection margins and perineural invasion were associated with disease recurrence. Pre-treatment methylated ctDNA measurement can improve the predictive value for recurrence in a subset of patients, particularly those with perineural involvement.

Registration: Australian and New Zealand Clinical Trials Registry #12611000318987.

背景:结直肠癌(CRC)的复发率很高,尤其是晚期患者,但根据手术分期和病理结果进行预后的效果有限。诊断时出现的循环肿瘤 DNA(ctDNA)可用于改善疾病复发的预测:评估诊断时检测甲基化 BCAT1/IKZF1 ctDNA 与人口统计学、生活方式、临床因素和肿瘤病理学相结合对复发预测价值的影响:设计:一项回顾性队列研究:该队列包括 180 名患者(36 名复发性 CRC 患者),他们接受了至少 3 年的完整治疗和监测。对复发和未复发患者的临床详情和ctDNA甲基化BCAT1/IKZF1结果进行比较,并通过cox回归分析评估各因素对无病生存率的影响:与无病生存率降低独立相关的临床因素包括结节受累(HR = 3.83,95% CI 1.56-9.43,P = .003)、M1 分期(HR = 4.41,95% CI 1.18-16.45,P = .027)、切除边缘小于 2 mm(HR = 4.60,95% CI 1.19-17.76,P = .027)、神经周围受累(HR = 2.50,95% CI 1.01-6.17,P = .047)和远端肿瘤(HR = 3.13,95% CI 1.07-9.18,P = .037)。在51.7%(93/180)的治疗前血浆样本中检测到甲基化的BCAT1/IKZF1。如果将ctDNA阳性结果与这些临床预后因素结合起来考虑,则神经周围受累(HR = 4.44,95% CI 1.92-10.26,P = .001)和远端肿瘤(HR = 5.04,95% CI 1.88-13.49,P = .001)患者的复发预测能力有所提高:结节侵犯、转移性疾病、远端肿瘤部位、切除边缘低和神经周围侵犯与疾病复发有关。治疗前甲基化ctDNA测量可提高对部分患者复发的预测价值,尤其是那些有神经周围受累的患者:澳大利亚和新西兰临床试验注册号:12611000318987。
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引用次数: 0
mRNA Expression and Methylation of the RAD51, ATM, ATR, BRCA1, and BRCA2 Genes in Gastric Adenocarcinoma. 胃腺癌中 RAD51、ATM、ATR、BRCA1 和 BRCA2 基因的 mRNA 表达和甲基化。
IF 3.4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-01-29 eCollection Date: 2024-01-01 DOI: 10.1177/11772719231225206
Joel Del Bel Pádua, Carolline Fontes Alves Mariano, Alexandre Todorovic Fabro, Fermino Sanches Lizarte Neto, Rogério Lenotti Zuliani, Cláudia Tarcila Gomes Sares, José Sebastião Dos Santos, Ajith Kumar Sankarankutty, Daniela Pretti da Cunha Tirapelli, Vanessa da Silva Silveira, Greice Andreotti de Molfetta, Wilson Araújo da Silva Júnior, Mariângela Ottoboni Brunaldi

Background: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers.

Objective and design: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm.

Methods: We evaluated mRNA expression and methylation of RAD51, ATM, ATR, BRCA1, and BRCA2 in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features.

Results: RAD51, ATR, BRCA1, BRCA2, and ATM mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: RAD51 with ATR (P = .027), BRCA1 (P < .001), and BRCA2 (P < .001); ATR with BRCA1 (P = .007), and ATM (P = .001); BRCA1 with BRCA2 (P = 0.001). BRCA1 mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, P = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, P = .035). Greater tumoral RAD51 mRNA levels correlated with perineural invasion (1.822 vs 0.725, P = .010) and death (1.664 vs 0.929, P = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, P = .032), and no significant correlation for the other markers.

Conclusions: Our results suggest RAD51, BRCA1, and BRCA2 methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced BRCA1 expression participates in disease progression, and show an association between RAD51 mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for ATR, can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.

背景:已知同源重组相关蛋白 RAD51、ATM、BRCA1 和 BRCA2 在胃腺癌(最致命的癌症之一)中的免疫组化预后意义:这项回顾性队列研究旨在评估该肿瘤中一些同源重组相关基因的 mRNA 表达和启动子甲基化情况:我们通过RT-qPCR和MS-HRM评估了胃切除术标本中肿瘤和非肿瘤冷冻样本中RAD51、ATM、ATR、BRCA1和BRCA2的mRNA表达和甲基化情况,并将我们的结果与之前的免疫组化数据和预后特征相关联:93.75%(45/48)、93.75%(45/48)、91.67%(44/48)、83.33%(40/48)和89.58%(43/48)的肿瘤检测到RAD51、ATR、BRCA1、BRCA2和ATM mRNA表达;94.87%(37/39)、0(0/42)、97.56%(40/41)、100%(41/41)和0(0/40)的肿瘤检测到部分或完全甲基化。大多数基因对之间的肿瘤 mRNA 表达呈明显的弱至中度正相关:RAD51 与 ATR(P = 0.027)、BRCA1(P BRCA2(P ATR 与 BRCA1(P = 0.007)和 ATM(P = 0.001);BRCA1 与 BRCA2(P = 0.001)。与非肿瘤性粘膜相比,肿瘤中的 BRCA1 mRNA 减少(0.345 vs 1.272,P = .015);除新辅助治疗病例外,T3 至 T4 肿瘤中的 BRCA1 mRNA 减少(0.414 vs 0.954,P = .035)。肿瘤RAD51 mRNA水平升高与神经周围侵犯(1.822 vs 0.725,P = .010)和死亡(1.664 vs 0.929,P = .036)相关,但与生存时间无关。ATR的核免疫组化阳性与mRNA水平呈反向关系(0.487 vs 0.907,P = .032),与其他标记物无显著相关性:我们的研究结果表明,RAD51、BRCA1 和 BRCA2 甲基化是胃癌中一种常见的表观遗传机制,支持 BRCA1 表达减少参与疾病进展的假设,并显示 RAD51 mRNA 与会厌浸润和死亡率之间存在关联,考虑到之前的免疫组化研究,这种关联可能被认为是出乎意料的。免疫组化与 mRNA 之间缺乏相关性,甚至与 ATR 呈反向关系,这表明转录后或翻译后调控机制发挥作用,有待进一步研究。
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