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Role of CYP19A1 Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population. CYP19A1位点(rs28757157和rs3751591)在中国汉族缺血性卒中风险中的作用
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S404160
Kang Huang, Tianyi Ma, Qiang Li, Zanrui Zhong, Ting Qin, Yilei Zhou, Wei Zhang, Shilin Tang, Jianghua Zhong, Shijuan Lu

Introduction: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population.

Methods: 1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk.

Results: In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24.

Conclusion: The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.

简介:缺血性脑卒中是一种受遗传因素影响的多因素、多基因疾病。在这项研究中,我们探讨了CYP19A1单核苷酸多态性(snp)在中国人群IS中的作用。方法:本研究共纳入1302例受试者,其中对照组651例,病例651例。通过千人基因组计划数据库筛选CYP19A1的4个候选snp (rs28757157 C/T、rs3751592 C/T、rs3751591 G/A、rss59429575 C/T)。CYP19A1 snp与IS风险之间的关系采用logistic回归分析,比值比(OR)和95%置信区间(CIs)。假阳性报告概率(FPRP)分析进一步验证了阳性结果。采用多因素降维法(MDR)分析SNP-SNP的相互作用,预测其风险。结果:在本研究中,CYP19A1位点(rs28757157和rs3751591)与IS的发生有关。这两种变异使得60岁以上、吸烟者和饮酒者对IS的易感性增加。Rs28757157与女性、非吸烟者和BMI小于24的受试者发生IS的风险相关,rss59429575与男性和BMI大于24的受试者发生IS的风险相关。结论:本研究发现CYP19A1位点(rs28757157和rs3751591)与中国汉族人群is发病风险存在显著相关性,为进一步探索其在is发病机制中的具体作用提供了理论依据。
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引用次数: 0
High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma. DNTTIP1高表达预示透明细胞肾细胞癌预后不良。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S382843
Xuegang Wang, Weiquan Li, Ning Lou, Weiwei Han, Bo Hai, Wen Xiao, Xiaoping Zhang

Background: Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC.

Methods: Kaplan-Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC.

Results: DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC.

Conclusion: This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.

背景:透明细胞肾细胞癌(ccRCC)患者的侵袭和转移导致预后不良和死亡。据报道,脱氧核苷酸转移酶末端相互作用蛋白1 (DNTTIP1)可促进多发性肿瘤的进展。然而,目前还没有关于DNTTIP1在ccRCC中的研究。方法:通过Kaplan-Meier生存分析、多因素分析,验证了肿瘤基因组图谱肾透明细胞癌(TCGA-KIRC)中DNTTIP1表达的ccRCC的预后指标总生存期(OS)和无病生存期(DFS)。ROC曲线分析DNTTIP1在TCGA-KIRC和验证数据集中的诊断能力。采用实时定量聚合酶链反应(qRT-PCR)检测DNTTIP1在肾癌组织中的表达,并由美国癌症临床蛋白质组学研究办公室(Office of cancer Clinical Proteomics Research, CPTAC)验证DNTTIP1的蛋白表达。此外,nomogram预测了DNTTIP1在ccRCC患者中的作用。单样本基因集富集分析(SsGSEA)和GSEA评估了DNTTIP1在TCGA-KIRC中的发病机制。结果:DNTTIP1在ccRCC肿瘤组织中表达较高。DNTTIP1高表达与不良OS (HR = 1.618, P < 0.0001)和不良DFS (HR = 1.789, P < 0.0001)相关。SsGSEA和GSEA显示DNTTIP1与缺氧、上皮-间质转化(EMT)、血管生成、G2M检查点相关。DNTTIP1与ccRCC中EMT生物标志物呈正相关,可能是ccRCC的有效靶点。结论:本研究提示DNTTIP1的高表达预示着ccRCC的不良预后,DNTTIP1可能是未来肿瘤恶性的新的检测生物标志物和治疗靶点。
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引用次数: 0
Resistance to PARP Inhibitors After First-Line Platinum-Based Chemotherapy in a Patient with Advanced Ovarian Cancer with a Pathogenic Somatic BRCA1 Mutation. 伴有致病性体细胞BRCA1突变的晚期卵巢癌患者在一线铂类化疗后对PARP抑制剂的耐药性
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S397827
Lan Zhong, Rutie Yin, Liang Song

PARP inhibitors (PARPi) are the maintenance therapy after first line platinum-based chemotherapy for patients with advanced epithelial ovarian cancer (EOC) with germline and pathogenic somatic BRCA1/2 mutations. However, as with chemotherapy, patients can develop resistance to PARPi. The selective pressure generated by heterogeneous somatic BRCA mutations may give rise to chemotherapy or PARPi resistant tumors. Here, we present the case of a patient harboring a pathogenic p.Glu143* (c.427G>T) somatic BRCA1 mutation conferring resistance to olaparib following cytoreductive surgery and platinum-based chemotherapy. We ordered a plasma ctDNA analysis (tissue biopsy of recurrent lesions was contraindicated due to their anatomical location) to figure out the possible resistance mechanism. Analysis of ctDNA did not detect the pathogenic somatic BRCA1 p.Glu143* (c.427G>T) mutation seen before. The tumor cells harboring the pathogenic BRCA1 mutation were probably eliminated by the platinum-based chemotherapy, leaving only those without BRCA mutations to proliferate.

PARP抑制剂(PARPi)是伴有生殖系和致病性BRCA1/2体细胞突变的晚期上皮性卵巢癌(EOC)患者一线铂类化疗后的维持治疗。然而,与化疗一样,患者可能对PARPi产生耐药性。异质体细胞BRCA突变产生的选择压力可能导致化疗或PARPi耐药肿瘤。在这里,我们提出了一个病例,患者携带致病性p.Glu143* (c.427G>T)体细胞BRCA1突变,在细胞减少手术和铂基化疗后对奥拉帕尼产生耐药性。我们要求进行血浆ctDNA分析(复发病变的组织活检由于其解剖位置是禁忌的),以找出可能的耐药机制。ctDNA分析未检测到之前发现的致病性体细胞BRCA1 p.g u143* (c.427G>T)突变。携带致病性BRCA1突变的肿瘤细胞可能被铂类化疗消除,只留下没有BRCA突变的肿瘤细胞增殖。
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引用次数: 0
Identification and Validation of Ferroptosis-Related Subtypes and a Predictive Signature in Hepatocellular Carcinoma. 肝细胞癌中铁中毒相关亚型的鉴定和验证及其预测特征。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S397892
Chunlan Zheng, Yanan Peng, Haizhou Wang, Youwei Wang, Lan Liu, Qiu Zhao

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with an immunosuppressive Tumor microenvironment (TME). Ferroptosis plays an essential role in tumor proliferation, invasion, and metastasis. However, the relationship between ferroptosis and TME of HCC has remained elusive.

Methods: Differentially expressed ferroptosis-related genes (DE FRGs) between normal liver tissues and HCC tissues were obtained from The Cancer Genome Atlas (TCGA). On this basis, we identified the molecular subtypes mediated by DE FRGs and TME cell infiltration. Next, a predictive signature was established to quantity the ferroptosis-related characteristics by performing the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivariate COX analyses determined the independent prognostic factors. Finally, the expression stability of 3 ferroptosis-related signature genes was verified in cancer and paracancerous normal tissues of HCC.

Results: We identified three different molecular subtypes and found that the subtype with the better prognosis was associated with high enrichment of immune- and metabolic-related hallmark signaling pathways and high infiltration of immune cells in TME. The signature was considered to be an independent prognostic factor. We also found that the signature can reflect the infiltration characteristics of different immune cells in TME. Immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), regulatory T cells, and type 17 T helper cells were significantly enriched in the high-risk group. The analysis data of immune checkpoints and tumor mutation load indicated that the signature had great potential in predicting Immunotherapy response and chemotherapeutic sensitivity. In addition, the overexpression of 3 ferroptosis-related signature genes was confirmed in HCC tissues and HCC cell lines. Ferroptosis inducer RSL3 inhibited the proliferation of HCC cells and was a potential cancer immunotherapy agent.

Conclusion: These findings enhanced our understanding of the regulatory mechanism of ferroptosis in HCC and provided new insights into evaluating prognosis and developing more effective Immunotherapy and chemotherapy strategies.

背景:肝细胞癌(HCC)是世界上最常见的恶性肿瘤之一,具有免疫抑制肿瘤微环境(TME)。铁下垂在肿瘤的增殖、侵袭和转移中起着重要的作用。然而,铁下垂与肝癌TME之间的关系尚不明确。方法:从癌症基因组图谱(TCGA)中获取正常肝组织与HCC组织间差异表达的铁中毒相关基因(DE FRGs)。在此基础上,我们确定了DE FRGs和TME细胞浸润介导的分子亚型。接下来,通过执行最小绝对收缩和选择算子Cox回归分析,建立了预测特征,以量化铁衰相关特征。单因素和多因素COX分析确定了独立的预后因素。最后,我们验证了3个铁中毒相关特征基因在HCC癌及癌旁正常组织中的表达稳定性。结果:我们鉴定出三种不同的分子亚型,发现预后较好的亚型与TME中免疫和代谢相关标志信号通路的高富集和免疫细胞的高浸润有关。该特征被认为是一个独立的预后因素。我们还发现该特征可以反映TME中不同免疫细胞的浸润特征。免疫抑制细胞,如髓源性抑制细胞(MDSCs)、调节性T细胞和17型T辅助细胞在高危组中显著富集。免疫检查点和肿瘤突变负荷的分析数据表明,该标记在预测免疫治疗反应和化疗敏感性方面具有很大的潜力。此外,在HCC组织和HCC细胞系中证实了3个铁中毒相关特征基因的过表达。铁下垂诱导剂RSL3可抑制肝癌细胞的增殖,是一种潜在的肿瘤免疫治疗药物。结论:这些发现增强了我们对肝癌铁下垂的调控机制的认识,为肝癌预后评估和制定更有效的免疫治疗和化疗策略提供了新的见解。
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引用次数: 2
Anlotinib Enhances the Therapeutic Effect of Bladder Cancer with GSDMB Expression: Analyzed from TCGA Bladder Cancer Database & Mouse Bladder Cancer Cell Line. Anlotinib增强膀胱癌GSDMB表达的治疗效果——来自TCGA膀胱癌数据库和小鼠膀胱癌细胞株的分析
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S398451
Chen Wang, Qifeng Cao, Shun Zhang, Hailong Liu, Huangqi Duan, Weimin Xia, Haibo Shen, Cheng Wang

Introduction and objective: The mitogen-activated protein kinase (MAPK) pathway is inhibited by the pan-target inhibitor Anlotinib, which induces tumor cell death. In addition to the common apoptosis and necrosis, there is also a pyroptosis mode of cancer cell death in recent years, which is mainly manifested by the cleavage of gasdermin proteins (GSDMs). Gasdermin B (GSDMB) participates in the progression and outcome of bladder cancer. The efficacy and mechanism of Anlotinib in the treatment of GSDMB-positive bladder tumors have not been studied to date.

Methods: The relationship between GSDMB expression and tumor stage, overall survival rate, immunotherapy response, tumor recurrence and progression rate was analyzed from the TCGA bladder cancer database. Anlotinib was used to treat GSDMB-positive bladder cancer in mice followed by flow analysis of the secretion of inflammatory factors related to pyroptosis and the level of anti-tumor factors. Western blot analysis detected which MAPK and MEK signal transduction pathways.

Results: TCGA data analysis showed that the overall survival rate of bladder cancer patients with high GSDMB expression was better than that of patients with low GSDMB expression. In vivo experiments showed that Anlotinib was more effective in the treatment of GSDMB-positive bladder cancer than GSDMB-negative bladder cancer. Anlotinib can increase the secretion of antitumor-related factors in GSDMB-positive bladder cancer such as TNF-a and CD107a. In addition, Anlotinib also induced an increase in GSDMB protein expression. Anlotinib treatment of GSDMB-positive bladder cancer decreased AKT and MEK protein expression, which were involved in Anlotinib signal transduction pathway.

Conclusion: Anlotinib has a strong antitumor effect on GSDMB-positive bladder tumors. This effect is mainly achieved by anlotinib stimulating the secretion of relevant antitumor factors by lymphocytes. The PI3K/AKT and MEK signal transduction pathways were inhibited by Anlotinib in bladder cancer expressing GSDMB protein.

简介与目的:丝裂原活化蛋白激酶(MAPK)通路被泛靶点抑制剂Anlotinib抑制,诱导肿瘤细胞死亡。除了常见的凋亡和坏死外,近年来还出现了一种肿瘤细胞死亡的焦亡模式,主要表现为gasdermin蛋白(GSDMs)的裂解。Gasdermin B (GSDMB)参与膀胱癌的进展和预后。Anlotinib治疗gsdmb阳性膀胱肿瘤的疗效及作用机制至今未见研究。方法:从TCGA膀胱癌数据库中分析GSDMB表达与肿瘤分期、总生存率、免疫治疗应答、肿瘤复发及进展率的关系。应用Anlotinib治疗小鼠gsdmb阳性膀胱癌,然后流式分析与焦亡相关的炎性因子分泌及抗肿瘤因子水平。Western blot分析检测了MAPK和MEK信号转导通路。结果:TCGA数据分析显示,GSDMB高表达膀胱癌患者的总生存率优于GSDMB低表达膀胱癌患者。体内实验表明,Anlotinib治疗gsdmb阳性膀胱癌比gsdmb阴性膀胱癌更有效。Anlotinib可增加gsdmb阳性膀胱癌中TNF-a、CD107a等抗肿瘤相关因子的分泌。此外,Anlotinib还诱导GSDMB蛋白表达增加。安洛替尼治疗gsdmb阳性膀胱癌可降低参与安洛替尼信号转导通路的AKT和MEK蛋白的表达。结论:安洛替尼对gsdmb阳性膀胱肿瘤具有较强的抗肿瘤作用。这种作用主要是通过anlotinib刺激淋巴细胞分泌相关抗肿瘤因子来实现的。在表达GSDMB蛋白的膀胱癌中,Anlotinib可抑制PI3K/AKT和MEK信号转导通路。
{"title":"Anlotinib Enhances the Therapeutic Effect of Bladder Cancer with GSDMB Expression: Analyzed from TCGA Bladder Cancer Database & Mouse Bladder Cancer Cell Line.","authors":"Chen Wang,&nbsp;Qifeng Cao,&nbsp;Shun Zhang,&nbsp;Hailong Liu,&nbsp;Huangqi Duan,&nbsp;Weimin Xia,&nbsp;Haibo Shen,&nbsp;Cheng Wang","doi":"10.2147/PGPM.S398451","DOIUrl":"https://doi.org/10.2147/PGPM.S398451","url":null,"abstract":"<p><strong>Introduction and objective: </strong>The mitogen-activated protein kinase (MAPK) pathway is inhibited by the pan-target inhibitor Anlotinib, which induces tumor cell death. In addition to the common apoptosis and necrosis, there is also a pyroptosis mode of cancer cell death in recent years, which is mainly manifested by the cleavage of gasdermin proteins (GSDMs). Gasdermin B (GSDMB) participates in the progression and outcome of bladder cancer. The efficacy and mechanism of Anlotinib in the treatment of GSDMB-positive bladder tumors have not been studied to date.</p><p><strong>Methods: </strong>The relationship between GSDMB expression and tumor stage, overall survival rate, immunotherapy response, tumor recurrence and progression rate was analyzed from the TCGA bladder cancer database. Anlotinib was used to treat GSDMB-positive bladder cancer in mice followed by flow analysis of the secretion of inflammatory factors related to pyroptosis and the level of anti-tumor factors. Western blot analysis detected which MAPK and MEK signal transduction pathways.</p><p><strong>Results: </strong>TCGA data analysis showed that the overall survival rate of bladder cancer patients with high GSDMB expression was better than that of patients with low GSDMB expression. In vivo experiments showed that Anlotinib was more effective in the treatment of GSDMB-positive bladder cancer than GSDMB-negative bladder cancer. Anlotinib can increase the secretion of antitumor-related factors in GSDMB-positive bladder cancer such as TNF-a and CD107a. In addition, Anlotinib also induced an increase in GSDMB protein expression. Anlotinib treatment of GSDMB-positive bladder cancer decreased AKT and MEK protein expression, which were involved in Anlotinib signal transduction pathway.</p><p><strong>Conclusion: </strong>Anlotinib has a strong antitumor effect on GSDMB-positive bladder tumors. This effect is mainly achieved by anlotinib stimulating the secretion of relevant antitumor factors by lymphocytes. The PI3K/AKT and MEK signal transduction pathways were inhibited by Anlotinib in bladder cancer expressing GSDMB protein.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"219-228"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/8a/pgpm-16-219.PMC10029935.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9171994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
miR-139-5p and miR-451a as a Diagnostic Biomarker in LUSC. miR-139-5p和miR-451a作为LUSC的诊断性生物标志物。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S402750
Bo Gao, Rui Li, Xiaojia Song, Shan Hu, Fengmei Yang

Background: Lung squamous cell carcinoma (LUSC) is a type of lung cancer that originates from segmental or subsegmental bronchial mucosa. There is evidence that miRNA plays an important role in the occurrence and progression of tumors.

Methods: In this study, plasma samples of patients with early LUSC and healthy volunteers were subjected to miRNA sequencing, and the levels of differentially expressed miRNAs (DEMs) in LUSC tissues were analyzed using R language. Cox regression and Kaplan-Meier (K-M) survival curve analyses were performed to determine the relationship between DEMs and prognosis in LUSC, and PCR method was verified for the plasma expression level of DEMs in patients with LUSC. The levels of CYFRA21-1 and SCC-Ag in plasma were measured, and area under curve (AUC) was used to evaluate the diagnostic value of the DEMs.

Results: A total of 21 DEMs were screened out by sequencing. The expression levels of DEMs in tissue samples in the TCGA database were analyzed, and four DEMs with consistent expression levels were further screened from plasma and tissue samples. Regression analysis and K-M curve were performed to select two DEMs (miR-139-5p, miR-451a) that were correlated with the prognosis. PCR verification results showed that the levels of miR-451a and miR-139-5p were low in patients, and the level of miR-139-5p in late stages III & IV with the patients of LUSC was higher than that in stages I & II. The AUC values of the four indicators (SCC-Ag, CYFRA21-1, miR-451a and miR-139-5p) in the diagnosis of LUSC, early and late cases were 0.884, 0.935 and 0.778, respectively.

Conclusion: The detection of miR-139-5p and miR-451a levels in plasma has a certain potential in the non-invasive diagnosis, especially in patients with early stages of LUSC.

背景:肺鳞状细胞癌(Lung squamous cell carcinoma, LUSC)是一种起源于支气管节段性或亚节段性粘膜的肺癌。有证据表明,miRNA在肿瘤的发生和发展中起着重要作用。方法:本研究对早期LUSC患者和健康志愿者的血浆样本进行miRNA测序,并使用R语言分析LUSC组织中差异表达的miRNA (DEMs)水平。采用Cox回归和Kaplan-Meier (K-M)生存曲线分析确定LUSC患者dem与预后的关系,并验证PCR法检测LUSC患者血浆中dem的表达水平。测定血浆CYFRA21-1和SCC-Ag水平,用曲线下面积(AUC)评价dem的诊断价值。结果:测序共筛选到21个dem。分析TCGA数据库组织样本中dem的表达水平,并进一步从血浆和组织样本中筛选出表达水平一致的4个dem。通过回归分析和K-M曲线选择与预后相关的两个dem (miR-139-5p、miR-451a)。PCR验证结果显示,miR-451a和miR-139-5p在患者中水平较低,且在LUSC患者的III、IV期晚期miR-139-5p水平高于I、II期。SCC-Ag、CYFRA21-1、miR-451a、miR-139-5p四项指标诊断LUSC、早期、晚期的AUC值分别为0.884、0.935、0.778。结论:检测血浆中miR-139-5p和miR-451a水平在无创诊断中具有一定的潜力,特别是在早期LUSC患者中。
{"title":"miR-139-5p and miR-451a as a Diagnostic Biomarker in LUSC.","authors":"Bo Gao,&nbsp;Rui Li,&nbsp;Xiaojia Song,&nbsp;Shan Hu,&nbsp;Fengmei Yang","doi":"10.2147/PGPM.S402750","DOIUrl":"https://doi.org/10.2147/PGPM.S402750","url":null,"abstract":"<p><strong>Background: </strong>Lung squamous cell carcinoma (LUSC) is a type of lung cancer that originates from segmental or subsegmental bronchial mucosa. There is evidence that miRNA plays an important role in the occurrence and progression of tumors.</p><p><strong>Methods: </strong>In this study, plasma samples of patients with early LUSC and healthy volunteers were subjected to miRNA sequencing, and the levels of differentially expressed miRNAs (DEMs) in LUSC tissues were analyzed using R language. Cox regression and Kaplan-Meier (K-M) survival curve analyses were performed to determine the relationship between DEMs and prognosis in LUSC, and PCR method was verified for the plasma expression level of DEMs in patients with LUSC. The levels of CYFRA21-1 and SCC-Ag in plasma were measured, and area under curve (AUC) was used to evaluate the diagnostic value of the DEMs.</p><p><strong>Results: </strong>A total of 21 DEMs were screened out by sequencing. The expression levels of DEMs in tissue samples in the TCGA database were analyzed, and four DEMs with consistent expression levels were further screened from plasma and tissue samples. Regression analysis and K-M curve were performed to select two DEMs (miR-139-5p, miR-451a) that were correlated with the prognosis. PCR verification results showed that the levels of miR-451a and miR-139-5p were low in patients, and the level of miR-139-5p in late stages III & IV with the patients of LUSC was higher than that in stages I & II. The AUC values of the four indicators (SCC-Ag, CYFRA21-1, miR-451a and miR-139-5p) in the diagnosis of LUSC, early and late cases were 0.884, 0.935 and 0.778, respectively.</p><p><strong>Conclusion: </strong>The detection of miR-139-5p and miR-451a levels in plasma has a certain potential in the non-invasive diagnosis, especially in patients with early stages of LUSC.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"313-323"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/7a/pgpm-16-313.PMC10093518.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9309477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Identification of Two Novel Variants of the DMD Gene in Chinese Families with Duchenne Muscular Dystrophy. 中国杜氏肌营养不良症家族DMD基因两个新变异的鉴定。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S416294
Jiangfen Wu, Lingyan Ren, Xinyi Huang, Li Hu, Liangliang Zhang, Dan Xie, Zhimin Li, Naijian Han, Shengwen Huang

Background: Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder, is caused by pathogenic variants in the DMD gene encoding a large structural protein in muscle cells.

Methods: Two probands, a 6-year old boy and a 1-month old infant, respectively, were clinically diagnosed with DMD based on elevated levels of creatine kinase and creatine kinase isoenzyme. CNVplex and whole exome sequencing (WES) were performed for causal variants, and Sanger sequencing was used for verification.

Results: CNVplex found no large deletions or duplications in the DMD gene in both patients, but WES discovered a single-nucleotide deletion in exon 48 (NM_004006.2:c.6963del, p.Asp2322ThrfsTer16) in the proband of pedigree 1, and a nonsense mutation in exon 27 (NM_004006.2:c.3637A>T, p.K1213Ter) in the proband of pedigree 2.

Conclusion: The results of our study expand the mutation spectrum of DMD and enrich our understanding of the clinical characteristics of DMD. Genetic counseling was provided for the two families involved in this study.

背景:杜氏肌营养不良症(DMD)是一种x连锁的隐性神经肌肉疾病,是由编码肌肉细胞中一个大结构蛋白的DMD基因的致病性变异引起的。方法:根据肌酸激酶和肌酸激酶同工酶水平升高,对2例6岁男童和1月龄婴儿进行临床诊断。对因果变异进行CNVplex和全外显子组测序(WES),并使用Sanger测序进行验证。结果:CNVplex在两例患者中均未发现DMD基因的大缺失或重复,但WES在48外显子(NM_004006.2:c)上发现了单核苷酸缺失。在第1家系先显子(NM_004006.2:c)中存在无义突变(NM_004006.2:c)。3637A>T, p.K1213Ter)系2先证者。结论:本研究结果拓展了DMD的突变谱,丰富了我们对DMD临床特征的认识。为参与本研究的两个家庭提供了遗传咨询。
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引用次数: 0
Personalized Dietary Regimens for Inflammatory Bowel Disease: Current Knowledge and Future Perspectives. 炎症性肠病的个性化饮食方案:目前的知识和未来的展望。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S359365
Judith Wellens, Eva Vissers, Christophe Matthys, Séverine Vermeire, João Sabino

Inflammatory bowel diseases (IBD) are chronic and incurable conditions of the gastro-intestinal tract with an increasing incidence and prevalence worldwide. Common symptoms are abdominal pain, diarrhea, and weight loss. Despite recent advances in medical management, many patients fail to achieve clinical remission and healing of the mucosa of the bowel. The cause is thought to involve an inappropriate reaction of the immune system, the microbiome and the environment in genetically susceptible individuals, leading to chronic bowel inflammation. Evidence is emerging that diet is a key environmental factor that might influence disease onset and course, and therefore may become a therapeutic strategy to mitigate inflammation and symptoms. Since IBD is a heterogeneous disease on a clinical and a molecular level, personalizing dietary advice could be the crucial factor to achieve long-lasting changes in dietary behaviors that could not only improve nutritional status but also tackle gut inflammation and abdominal symptoms on an individual level. In this review, we first discuss different aspects of personalized nutrition, namely the level, focus, and scope of personalized dietary regimens. Then, we provide a framework for the different goals of nutritional therapy in IBD and current evidence for personalized dietary approaches. Lastly, we discuss the need for adequate trial designs, access to the right data types and the bioinformatic tools that are necessary to develop algorithms that will allow us to move from general "healthy eating" advice to truly personalized nutritional plans for the individual IBD patient.

炎症性肠病(IBD)是一种慢性且无法治愈的胃肠道疾病,在世界范围内的发病率和患病率不断上升。常见的症状是腹痛、腹泻和体重减轻。尽管最近在医疗管理方面取得了进展,但许多患者未能达到临床缓解和肠粘膜愈合。其原因被认为与免疫系统、微生物群和遗传易感个体的环境的不适当反应有关,从而导致慢性肠道炎症。越来越多的证据表明,饮食是可能影响疾病发病和病程的关键环境因素,因此可能成为减轻炎症和症状的治疗策略。由于IBD在临床和分子水平上是一种异质性疾病,个性化的饮食建议可能是实现饮食行为长期改变的关键因素,这不仅可以改善营养状况,还可以在个体水平上解决肠道炎症和腹部症状。在这篇综述中,我们首先讨论了个性化营养的不同方面,即个性化饮食方案的水平、重点和范围。然后,我们为IBD营养治疗的不同目标和个性化饮食方法的当前证据提供了一个框架。最后,我们讨论了适当的试验设计的必要性,获得正确的数据类型和开发算法所必需的生物信息学工具,这些算法将使我们能够从一般的“健康饮食”建议转向针对个体IBD患者的真正个性化的营养计划。
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引用次数: 2
Drug-Drug-Gene Interactions in Cardiovascular Medicine. 心血管医学中的药物-药物-基因相互作用》。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-11-02 eCollection Date: 2022-01-01 DOI: 10.2147/PGPM.S338601
Innocent G Asiimwe, Munir Pirmohamed

Cardiovascular disease remains a leading cause of both morbidity and mortality worldwide. It is widely accepted that both concomitant medications (drug-drug interactions, DDIs) and genomic factors (drug-gene interactions, DGIs) can influence cardiovascular drug-related efficacy and safety outcomes. Although thousands of DDI and DGI (aka pharmacogenomic) studies have been published to date, the literature on drug-drug-gene interactions (DDGIs, cumulative effects of DDIs and DGIs) remains scarce. Moreover, multimorbidity is common in cardiovascular disease patients and is often associated with polypharmacy, which increases the likelihood of clinically relevant drug-related interactions. These, in turn, can lead to reduced drug efficacy, medication-related harm (adverse drug reactions, longer hospitalizations, mortality) and increased healthcare costs. To examine the extent to which DDGIs and other interactions influence efficacy and safety outcomes in the field of cardiovascular medicine, we review current evidence in the field. We describe the different categories of DDIs and DGIs before illustrating how these two interact to produce DDGIs and other complex interactions. We provide examples of studies that have reported the prevalence of clinically relevant interactions and the most implicated cardiovascular medicines before outlining the challenges associated with dealing with these interactions in clinical practice. Finally, we provide recommendations on how to manage the challenges including but not limited to expanding the scope of drug information compendia, interaction databases and clinical implementation guidelines (to include clinically relevant DDGIs and other complex interactions) and work towards their harmonization; better use of electronic decision support tools; using big data and novel computational techniques; using clinically relevant endpoints, preemptive genotyping; ensuring ethnic diversity; and upskilling of clinicians in pharmacogenomics and personalized medicine.

心血管疾病仍然是全球发病率和死亡率的主要原因。人们普遍认为,并用药物(药物-药物相互作用,DDIs)和基因组因素(药物-基因相互作用,DGIs)都会影响心血管药物的疗效和安全性。尽管迄今为止已发表了数以千计的 DDI 和 DGI(又称药物基因组学)研究,但有关药物与药物基因相互作用(DDGIs,DDIs 和 DGIs 的累积效应)的文献仍然很少。此外,心血管疾病患者多病共存的情况很常见,而且往往与多种药物治疗有关,这增加了临床相关药物相互作用的可能性。这反过来又会导致药物疗效降低、药物相关伤害(药物不良反应、住院时间延长、死亡率)和医疗成本增加。为了研究 DDGIs 和其他相互作用对心血管医学领域疗效和安全结果的影响程度,我们回顾了该领域的现有证据。我们描述了 DDIs 和 DGIs 的不同类别,然后说明了这两者如何相互作用产生 DDGIs 和其他复杂的相互作用。我们提供了一些研究实例,这些研究报告了临床相关相互作用的普遍性以及牵连最大的心血管药物,然后概述了在临床实践中处理这些相互作用所面临的挑战。最后,我们就如何应对挑战提出了建议,包括但不限于:扩大药物信息汇编、相互作用数据库和临床实施指南的范围(纳入临床相关的 DDGIs 和其他复杂相互作用),并努力使其协调一致;更好地使用电子决策支持工具;使用大数据和新型计算技术;使用临床相关终点、先期基因分型;确保种族多样性;以及提高临床医师在药物基因组学和个性化医疗方面的技能。
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引用次数: 0
Examining an Association of Single Nucleotide Polymorphisms with Hyperuricemia in Chinese Flight Attendants 中国空乘人员单核苷酸多态性与高尿酸血症的关系研究
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-06-08 DOI: 10.2147/PGPM.S364206
Jianpin Ye, Zhiwei Zeng, Yuxian Chen, Zhenkun Wu, Qingwei Yang, Tao Sun
Background Both genetic and environmental factors strongly affect serum uric acid (SUA) concentrations. The incidence of hyperuricemia tends to be younger in the Chinese population. In particular, we have found a high prevalence of hyperuricemia among Chinese flight attendants, aged from 20 to 40, in our survey. This study aims to evaluate whether there is an association between gene polymorphisms and hyperuricemia among Chinese flight attendants. Methods A total of 532 flight attendants with high and normal serum uric acid levels were recruited. Allele-specific polymerase chain reaction (AS-PCR) was performed using blood samples of enrolled subjects. Results Previous studies have reported single nucleotide polymorphisms (SNPs) that are tightly associated with uric acid levels. Among them, six SNPs that are strongly associated with SUA or gout in Asians, for instance ABCG2 (rs2231142, rs72552713 and rs2231137), GCKR (rs780094), SLC2A9 (rs1014290) and SLC17A1 (rs1183201), were selected for AS-PCR analyses. We found that SNPs such as ABCG2 rs2231142, GCKR rs780094 and SLC2A9 rs1014290 are strongly associated with hyperuricemia in male flight attendants, and SLC2A9 rs1014290 among female flight attendants. Conclusion Our study provides evidences of an association between SNPs and hyperuricemia in the Chinese flight attendants, and highlights the significance of improving diagnostics and prevention of disease development in uric acid metabolism disorders and gout using these SNPs.
背景遗传和环境因素都强烈影响血清尿酸(SUA)浓度。高尿酸血症的发病率在中国人群中趋于年轻化。特别是,在我们的调查中,我们发现20至40岁的中国乘务员高尿酸血症的患病率很高。本研究旨在评估中国乘务员的基因多态性与高尿酸血症之间是否存在关联。方法对532名血清尿酸水平高、正常的乘务员进行调查。使用入选受试者的血液样本进行等位基因特异性聚合酶链反应(AS-PCR)。结果已有研究报道单核苷酸多态性(SNPs)与尿酸水平密切相关。其中,选择6个与亚洲人SUA或痛风密切相关的SNPs,例如ABCG2(rs2231142、rs72552713和rs2231137)、GCKR(rs780094)、SLC2A9(rs1014290)和SLC17A1(rs1183201)进行AS-PCR分析。我们发现ABCG2 rs2231142、GCKR rs780094和SLC2A9 rs1014290等SNPs与男性空乘人员的高尿酸血症密切相关,而SLC2A9s 1014290与女性空乘人员密切相关。结论我们的研究为中国空乘人员的SNPs与高尿酸血症之间的关系提供了证据,并强调了使用这些SNPs改善尿酸代谢紊乱和痛风的诊断和预防疾病发展的意义。
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引用次数: 1
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Pharmacogenomics & Personalized Medicine
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