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Circulating microRNAs as the achilles forte of diagnostics and prognostics in acute graft versus host disease following allogeneic hematopoietic stem cell transplantation 循环微RNA是异体造血干细胞移植后急性移植物抗宿主疾病诊断和预后的致命弱点
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-19 DOI: 10.1016/j.genrep.2024.102037
Marzieh Izadifard , Mohammad Ahmadvand , Kamran Alimoghadam , Hossein Pashaiefar , Ghazal Seghatoleslami , Maryam Barkhordar , Marjan Yaghmaie
Acute graft-versus-host disease (aGVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), a procedure intended to treat malignant and nonmalignant hematological illnesses. At this time, there are no laboratory tests that can accurately forecast the likelihood of developing aGVHD, a patient's response to treatment, or their chance of life. Encouragingly, specific microRNAs have demonstrated consistent connections with the onset, severity, and clinical consequences of aGVHD through their dysregulated expression patterns, providing potential advantages in patient management and individualized therapy plans. Additionally, minimally invasive diagnostic methods are made easier by identification and measurement of circulating microRNAs as biomarkers in bodily fluids such as blood or urine using high-throughput screening techniques like qPCR, microarray analysis, and next-generation sequencing. Regarding the diagnosis, prognosis, and therapeutic response, this review is concentrated on the most recent research that offer proof of the possible utility of circulating microRNAs in blood and other bodily fluids as minimally invasive biomarkers of aGVHD. In addition to being useful tools for enhancing aGVHD management and patient outcomes, microRNAs distinctive expression patterns and functions in disease biology also present prospects for personalized medicine.
急性移植物抗宿主疾病(aGVHD)是异基因造血干细胞移植(allo-HSCT)后常见的并发症,这种手术旨在治疗恶性和非恶性血液病。目前,还没有任何实验室检测方法可以准确预测罹患异基因造血干细胞抗宿主疾病的可能性、患者对治疗的反应或存活机会。令人鼓舞的是,特定的 microRNA 通过其失调的表达模式与 aGVHD 的发病、严重程度和临床后果有着一致的联系,为患者管理和个体化治疗计划提供了潜在的优势。此外,利用 qPCR、微阵列分析和新一代测序等高通量筛选技术对血液或尿液等体液中作为生物标志物的循环 microRNA 进行鉴定和测量,可使微创诊断方法变得更加简便。在诊断、预后和治疗反应方面,本综述集中于最新的研究,这些研究证明了血液和其他体液中的循环 microRNA 可作为 aGVHD 的微创生物标志物。microRNA 除了是改善 aGVHD 管理和患者预后的有用工具外,其在疾病生物学中独特的表达模式和功能也为个性化医疗带来了前景。
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引用次数: 0
Missense variant rs75603675 within TMPRSS2 gene is associated with the increased risk of severe form of COVID-19 TMPRSS2 基因中的错义变异 rs75603675 与 COVID-19 重症型风险增加有关
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-18 DOI: 10.1016/j.genrep.2024.102039
Abdullah Al Saba , Jasmin Nur , Md Sohrab Alam , Zakir Hossain Howlader , Laila N. Islam , A.H.M. Nurun Nabi
Host genetics among other factors play an important role in COVID-19 disease severity. TMPRSS2, a serine protease, facilitates the priming of the SARS-CoV-2 spike protein, which is essential for the virus to enter the host cell. Several studies had targeted the TMPRSS2 polymorphisms with respect to SARS-CoV-2 infection and COVID-19 disease severity. Initially, the Whole Exome Sequencing (WES) of 7 healthy individuals and 22 COVID-19 patients with different degrees of disease severity was conducted to find the mutational landscape in different genes. A total of 26 single nucleotide polymorphisms (SNPs) were identified of which six were within the exons of TMPRSS2 (four synonymous and two nonsynonymous variants) while the rest of the 20 SNPs were recognized within the flanking intronic regions of TMPRSS2 gene. The nonsynonymous SNPs, rs75603675 and rs12329760, were further evaluated for association with disease severity in a larger sample size of 120 individuals by PCR followed by Sanger sequencing. Neither allelic nor genotypic distributions of rs12329760 were significantly associated with COVID-19 disease severity. However, individuals harboring the A allele of rs75603675 was found to have higher risk of severe COVID-19 compared to the C allele [OR (95%CI): 1.95 (1.11–3.39), p = 0.019]. Also, the genotype A/A [OR (95%CI): 5.13 (1.00–26.38), p = 0.033] of rs75603675 was associated with increased risk of severe COVID-19 under the recessive genetic inheritance model. Although the impact of COVID-19 pandemic has waned due to vaccination and public health measures, continued research on the association of COVID-19 disease severity and infection susceptibility with host genetics is required to shed valuable insights on the future long-term health effects of COVID-19 and impact of new variants on different populations and enable implication of proper informed healthcare strategies during future public health crises.
宿主遗传等因素对 COVID-19 疾病的严重程度起着重要作用。TMPRSS2是一种丝氨酸蛋白酶,能促进SARS-CoV-2尖峰蛋白的启动,而尖峰蛋白是病毒进入宿主细胞的必要条件。有几项研究针对 TMPRSS2 多态性与 SARS-CoV-2 感染和 COVID-19 疾病严重程度的关系进行了研究。最初,研究人员对 7 名健康人和 22 名病情严重程度不同的 COVID-19 患者进行了全外显子组测序(WES),以发现不同基因的突变情况。共鉴定出 26 个单核苷酸多态性(SNPs),其中 6 个在 TMPRSS2 的外显子中(4 个同义变异和 2 个非同义变异),其余 20 个 SNPs 在 TMPRSS2 基因的侧翼内含子区。非同义 SNPs(rs75603675 和 rs12329760)通过 PCR 和 Sanger 测序在 120 人的更大样本中进一步评估了与疾病严重程度的关联性。rs12329760的等位基因和基因型分布均与COVID-19疾病的严重程度无明显关联。然而,与 C 等位基因相比,携带 rs75603675 的 A 等位基因的个体罹患严重 COVID-19 的风险更高[OR (95%CI):1.95 (1.11-3.39),p = 0.019]。此外,在隐性遗传模式下,rs75603675 的基因型 A/A [OR (95%CI):5.13 (1.00-26.38),p = 0.033] 与严重 COVID-19 的风险增加有关。尽管由于疫苗接种和公共卫生措施的实施,COVID-19 大流行的影响已经减弱,但仍需继续研究 COVID-19 疾病严重程度和感染易感性与宿主遗传学的关联,以深入了解 COVID-19 对未来健康的长期影响以及新变异对不同人群的影响,并在未来公共卫生危机期间制定适当的知情医疗保健策略。
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引用次数: 0
Modulatory effects of sub-MIC concentrations silver nanoparticles on virulence factor gene expression in Staphylococcus aureus 亚中微子浓度银纳米粒子对金黄色葡萄球菌毒力因子基因表达的调节作用
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-16 DOI: 10.1016/j.genrep.2024.102034
Basireh Baei , Ezzat Allah Ghaemi , Naeme Javid

Background

Silver nanoparticles (AgNPs) exhibit a dose-dependent anti-bacterial effect, and it was aimed in this study to investigate the impact of sub-minimum inhibitory concentration (MIC) doses of AgNPs on the expression of virulence genes in Staphylococcus aureus (S. aureus).

Methods

Minimum inhibitory concentration (MIC) values for AgNPs were determined for 183 S. aureus isolates. Gene expression was assessed in 14 isolates with sea and seb genes treated with AgNPs at a sub-MIC dose of 1 μg/ml. Accordingly, these strains were exposed to 1 μg/ml doses of AgNPs, and gene expression levels of sea, seb, and agr were assessed using quantitative RT-PCR after 4- and 12-hour post-AgNPs inoculation at 37 °C. The impact of AgNPs on the virulence factors of S. aureus was investigated over different time points, focusing on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates.

Results

Analysis revealed significant reductions in gene expression levels of seb and agr after 4 h post-AgNPs treatment in the MSSA group (p < 0.05), with further decreases observed at 12 h for sea, seb, and agr genes (p < 0.0001). MRSA isolates exhibited significant declines in sea and agr gene expression levels at both time points (p < 0.0001). However, no significant changes were observed in seb gene expression among MRSA isolates. Fold-change analysis indicated time-dependent effects of AgNP treatment on gene expression, highlighting substantial alterations in gene expression levels over time, particularly in seb and agr genes.

Conclusion

These results show that sub-MIC levels of AgNPs greatly decrease the gene expression of important virulence factors in MSSA and MRSA strains, indicating their promise as treatments for S. aureus infections, particularly at 12 h post-treatment. The differential response between MSSA and MRSA isolates highlights the importance of strain variation in antimicrobial strategies.

背景银纳米粒子(AgNPs)具有剂量依赖性抗菌效果,本研究旨在探讨次最低抑菌浓度(MIC)剂量的 AgNPs 对金黄色葡萄球菌(S. aureus)毒力基因表达的影响。方法确定了 183 个金黄色葡萄球菌分离物的 AgNPs 最低抑菌浓度(MIC)值。对 14 个带有 sea 和 seb 基因的分离菌株进行了基因表达评估,AgNPs 的亚 MIC 剂量为 1 μg/ml。因此,将这些菌株暴露于 1 μg/ml 剂量的 AgNPs 中,在 37 °C 下接种 AgNPs 4 小时和 12 小时后,使用定量 RT-PCR 对 sea、seb 和 agr 的基因表达水平进行评估。研究了 AgNPs 在不同时间点对金黄色葡萄球菌毒力因子的影响,重点是甲氧西林敏感金黄色葡萄球菌(MSSA)和甲氧西林耐药金黄色葡萄球菌(MRSA)分离物。结果分析表明,AgNPs 处理后 4 小时,MSSA 组的 seb 和 agr 基因表达水平明显下降(p < 0.05),12 小时后,sea、seb 和 agr 基因表达水平进一步下降(p < 0.0001)。MRSA 分离物在两个时间点的 sea 和 agr 基因表达水平都出现了显著下降(p < 0.0001)。然而,在 MRSA 分离物中未观察到 seb 基因表达的明显变化。折叠变化分析表明,AgNP 处理对基因表达的影响具有时间依赖性,突显出基因表达水平随时间的推移发生了重大变化,尤其是 seb 和 agr 基因。MSSA 和 MRSA 分离物之间的不同反应凸显了菌株变异在抗菌策略中的重要性。
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引用次数: 0
Inhibitory effect of dendrosomal-nanocurcumin on Burkitt's lymphoma cells by reducing EBV lytic gene expression 通过减少 EBV 裂解基因的表达,树枝状蛋白-纳米古柯碱对伯基特淋巴瘤细胞具有抑制作用
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-16 DOI: 10.1016/j.genrep.2024.102035
Mahboobeh Cheragh , Masoud Parsania , Majid Sadeghizadeh , Mohammad Hassan Pouriayevali

Introduction

Epstein-Barr virus (EBV) is a human oncogenic virus that targets B lymphocytes and is associated with some malignancies, such as Burkitt's lymphoma. Curcumin, as a natural product, has anticancer, antiproliferative, and antiviral properties. The combination of curcumin with some nanoparticles, such as dendrosom, can increase its solubility and anti-cancer effects. The present research aims to investigate the antiviral effect of Dendrosomal NanoCurcumin (DNC) on Burkitt's lymphoma cells (Daudi cell line) and the expression of EBV lytic genes and apoptosis.

Materials and methods

The cytotoxicity of curcumin, DNC, and dendrosome on Daudi cells and Peripheral Blood Mononuclear Cells (PBMC) as a control was assessed using a (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) MTT assay. Cell apoptosis was evaluated by Annexin/PI flow cytometry. RNA expression of BZLF1, BHRF1, and BRLF1 was assessed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assay. The t-test was used for statistical analysis.

Results

The half-minimum concentration of cytotoxicity (CC50) for nanocurcumin was 30 μg/ml, for curcumin 50 μg/ml, and for dendrosome 987 μg/ml. DNC caused time and dose-dependent death in Daudi cancer cells compared to curcumin and showed no toxicity in control cells. Quantitative RT-PCR evaluation showed a significant decrease in BZLF1, BHRF1, and BRLF1 mRNA expression at 30 μg/ml concentration of DNC compared to the control. The data obtained from the relative measurement of gene expression showed a decrease in the expression of viral lytic genes (P < 0.001).

Conclusion

In this study, it is noted that carriers, such as dendrosome, enhance the bioavailability of curcumin, thereby increasing its antitumor properties and cell apoptosis. Noteworthy, DNC nanoparticles can serve as a promising drug candidate and supplement in the treatment of Burkitt's lymphoma and in improving patient survival by reducing the expression of EBV lytic phase viral genes.
导言天疱疮病毒(EBV)是一种针对 B 淋巴细胞的人类致癌病毒,与某些恶性肿瘤(如伯基特淋巴瘤)有关。姜黄素作为一种天然产品,具有抗癌、抗增殖和抗病毒的特性。姜黄素与一些纳米粒子(如石斛素)结合,可增加其溶解度和抗癌效果。本研究旨在探讨 Dendrosomal 纳米姜黄素(DNC)对伯基特淋巴瘤细胞(Daudi 细胞系)的抗病毒作用,以及 EBV 致死基因的表达和细胞凋亡。材料和方法姜黄素、DNC 和 Dendrosome 对 Daudi 细胞和作为对照的外周血单核细胞(PBMC)的细胞毒性采用(3-(4, 5-二甲基噻唑基-2)-2, 5-二苯基溴化四氮唑)MTT 法进行评估。细胞凋亡通过 Annexin/PI 流式细胞术进行评估。BZLF1、BHRF1和BRLF1的RNA表达通过实时定量反转录聚合酶链反应(qRT-PCR)进行评估。结果纳米姜黄素的半数最低细胞毒性浓度(CC50)为 30 μg/ml,姜黄素为 50 μg/ml,树突状细胞为 987 μg/ml。与姜黄素相比,DNC 对 Daudi 癌细胞造成的死亡具有时间和剂量依赖性,而对对照细胞则无毒性。定量 RT-PCR 评估显示,与对照组相比,浓度为 30 μg/ml 的 DNC 会显著降低 BZLF1、BHRF1 和 BRLF1 mRNA 的表达。基因表达的相对测量数据显示,病毒裂解基因的表达量有所下降(P < 0.001)。值得注意的是,DNC 纳米粒子可作为治疗伯基特淋巴瘤的候选药物和辅助药物,通过减少 EBV 溶核期病毒基因的表达,提高患者的生存率。
{"title":"Inhibitory effect of dendrosomal-nanocurcumin on Burkitt's lymphoma cells by reducing EBV lytic gene expression","authors":"Mahboobeh Cheragh ,&nbsp;Masoud Parsania ,&nbsp;Majid Sadeghizadeh ,&nbsp;Mohammad Hassan Pouriayevali","doi":"10.1016/j.genrep.2024.102035","DOIUrl":"10.1016/j.genrep.2024.102035","url":null,"abstract":"<div><h3>Introduction</h3><div>Epstein-Barr virus (EBV) is a human oncogenic virus that targets B lymphocytes and is associated with some malignancies, such as Burkitt's lymphoma. Curcumin, as a natural product, has anticancer, antiproliferative, and antiviral properties. The combination of curcumin with some nanoparticles, such as dendrosom, can increase its solubility and anti-cancer effects. The present research aims to investigate the antiviral effect of Dendrosomal NanoCurcumin (DNC) on Burkitt's lymphoma cells (Daudi cell line) and the expression of EBV lytic genes and apoptosis.</div></div><div><h3>Materials and methods</h3><div>The cytotoxicity of curcumin, DNC, and dendrosome on Daudi cells and Peripheral Blood Mononuclear Cells (PBMC) as a control was assessed using a (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) MTT assay. Cell apoptosis was evaluated by Annexin/PI flow cytometry. RNA expression of <em>BZLF1</em>, <em>BHRF1</em>, and <em>BRLF1</em> was assessed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assay. The <em>t</em>-test was used for statistical analysis.</div></div><div><h3>Results</h3><div>The half-minimum concentration of cytotoxicity (CC50) for nanocurcumin was 30 μg/ml, for curcumin 50 μg/ml, and for dendrosome 987 μg/ml. DNC caused time and dose-dependent death in Daudi cancer cells compared to curcumin and showed no toxicity in control cells. Quantitative RT-PCR evaluation showed a significant decrease in <em>BZLF1</em>, <em>BHRF1</em>, and <em>BRLF1</em> mRNA expression at 30 μg/ml concentration of DNC compared to the control. The data obtained from the relative measurement of gene expression showed a decrease in the expression of viral lytic genes (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>In this study, it is noted that carriers, such as dendrosome, enhance the bioavailability of curcumin, thereby increasing its antitumor properties and cell apoptosis. Noteworthy, DNC nanoparticles can serve as a promising drug candidate and supplement in the treatment of Burkitt's lymphoma and in improving patient survival by reducing the expression of EBV lytic phase viral genes.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102035"},"PeriodicalIF":1.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310968","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
Bioevaluation, pharmacokinetics and molecular docking study of terpenoid-rich rhizome essential oil of Zingiber officinale 富含萜类化合物的细辛根茎精油的生物评估、药代动力学和分子对接研究
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-15 DOI: 10.1016/j.genrep.2024.102027
Ananya Nayak, Ayushman Gadnayak, Chiranjibi Sahoo, Sudipta Jena, Asit Ray, Pratap Chandra Panda, Sanghamitra Nayak, Ambika Sahoo
The study focuses on the phytochemical composition, in vitro and in silico antioxidant and NO reduction potential of Zingiber Officinale rhizome essential oil (ZOREO). The GC–MS analysis has revealed the presence of 47 volatile constituents representing 94.35 % of the total area of EO. The major compounds identified were α-zingiberene (20.58 %), geranial (10 %), β-sesquiphellandrene (7.39 %), and neral (7.23 %). The EO was rich in sesquiterpene hydrocarbons (45.93 %) followed by monoterpene hydrocarbons (29.29 %). The EO showed moderate antioxidant activity compared to the standard (IC50 = 5.16 ± 0.4 mg/mL for DPPH assay and EC50 = 0.52 ± 0.6 mg/mL for FRAP assay). The cytotoxic analysis showed significant viability towards RAW 264.7 cell lines. Treatment with ginger EO at a concentration of 100 μg/mL showed significant anti-inflammatory activity by the significant reduction of LPS-induced nitric oxide (NO) production to 31.35 %, in comparison with the LPS-treated group. Further, the EO components were screened in order to provide mechanistic insights into Xanthine oxidase (XO) and iNOS inhibition. The docking results showed that the volatile constituents of ginger EO have substantial binding affinity with the active site residues of the receptor. The simulation conducted for the top compounds- geranyl acetate and β-eudesmol having the highest binding affinity towards both the proteins XO and iNOS respectively. Both the results showed the compounds steadily interacted with both of the proteins active site residues throughout the simulation. The current analysis showed the phytoconstituents showed better antioxidant activity than the EO. Hence these compounds could be further considered for in vitro and in vivo evaluation for the development of efficient phytopharmaceuticals.
本研究主要探讨了银杏根茎精油(ZOREO)的植物化学成分、体外和硅学抗氧化及还原氮氧化物的潜力。气相色谱-质谱(GC-MS)分析显示,精油中含有 47 种挥发性成分,占精油总面积的 94.35%。鉴定出的主要化合物为α-zingiberene(20.58 %)、geranial(10 %)、β-sesquiphellandrene(7.39 %)和 neral(7.23 %)。环氧乙烷富含倍半萜烃(45.93 %),其次是单萜烃(29.29 %)。与标准物质相比,环氧乙烷显示出适度的抗氧化活性(DPPH 试验的 IC50 = 5.16 ± 0.4 mg/mL,FRAP 试验的 EC50 = 0.52 ± 0.6 mg/mL)。细胞毒性分析表明,生姜对 RAW 264.7 细胞株有显著的活力。用浓度为 100 μg/mL 的生姜环氧乙烷处理后,与 LPS 处理组相比,LPS 诱导的一氧化氮(NO)产生显著减少了 31.35%,从而显示出明显的抗炎活性。此外,还对环氧乙烷成分进行了筛选,以深入了解黄嘌呤氧化酶(XO)和一氧化氮(iNOS)的抑制机理。对接结果表明,生姜环氧乙烷的挥发性成分与受体的活性位点残基有很强的结合亲和力。模拟结果表明,乙酸香叶酯和β-桉叶油醇这两种顶级化合物分别与 XO 和 iNOS 蛋白的结合亲和力最高。这两项结果都表明,在整个模拟过程中,这些化合物都与这两种蛋白质的活性位点残基发生了稳定的相互作用。目前的分析表明,植物成分的抗氧化活性优于环氧乙烷。因此,可以进一步考虑对这些化合物进行体外和体内评估,以开发高效的植物药物。
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引用次数: 0
Genetic predisposition to vitamin D deficiency in Indian athletes: Role of CYP2R1 rs10741657 variant 印度运动员维生素 D 缺乏的遗传易感性:CYP2R1 rs10741657 变异的作用
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-15 DOI: 10.1016/j.genrep.2024.102033
Kavanashri N.M. , Keren Harish Tiwari , Sandeep Kumar Kotturu , Dinesh Yadav D.M. , Sudip Ghosh , Venkata Ramana Yagnambhatt
Vitamin D deficiency can negatively impact the health and training efficiency of athletes. The rs10741657(G) allele in CYP2R1 gene has been associated with lower vitamin D status, potentially contributing to vitamin D deficiency observed across various populations, including Indians. This study aimed to investigate whether the CYP2R1 (rs10741657) polymorphism is contributing to the vitamin D status among Indian athletes. Blood samples were collected from 92 Indian elite and sub-elite athletes participating in weightlifting (29), badminton (32), athletics (14), and rowing (17) for laboratory analysis. PCR-RFLP of the CYP2R1 (rs10741657) SNP was performed, and vitamin D levels were measured. Statistical analysis was done to assess the association between genotype and vitamin D status. Vitamin D levels were comparable between genders but differed across sports, with indoor athletes, especially badminton players having higher levels. The AA genotype was associated with higher vitamin D levels compared to the GG and AG genotypes. Vitamin D deficiency is highly prevalent among the athletes studied. This deficiency may be due to the higher prevalence of the alternate allele (G) of CYP2R1 polymorphism, suggesting that genetic predisposition plays a key role in determining the vitamin D status of athletes.
维生素 D 缺乏会对运动员的健康和训练效率产生负面影响。CYP2R1基因中的rs10741657(G)等位基因与较低的维生素D状态有关,可能是包括印度人在内的不同人群维生素D缺乏的原因之一。本研究旨在调查 CYP2R1(rs10741657)多态性是否与印度运动员的维生素 D 状态有关。研究人员采集了 92 名参加举重(29 人)、羽毛球(32 人)、田径(14 人)和赛艇(17 人)的印度精英和亚精英运动员的血样进行实验室分析。对 CYP2R1 (rs10741657) SNP 进行了 PCR-RFLP,并测量了维生素 D 水平。统计分析评估了基因型与维生素 D 状态之间的关联。不同性别之间的维生素 D 水平相当,但不同运动项目之间存在差异,室内运动员,尤其是羽毛球运动员的维生素 D 水平更高。与 GG 和 AG 基因型相比,AA 基因型的维生素 D 水平更高。在所研究的运动员中,维生素 D 缺乏症非常普遍。这种缺乏可能是由于 CYP2R1 多态性的另一等位基因(G)的流行率较高,这表明遗传易感性在决定运动员的维生素 D 状态方面起着关键作用。
{"title":"Genetic predisposition to vitamin D deficiency in Indian athletes: Role of CYP2R1 rs10741657 variant","authors":"Kavanashri N.M. ,&nbsp;Keren Harish Tiwari ,&nbsp;Sandeep Kumar Kotturu ,&nbsp;Dinesh Yadav D.M. ,&nbsp;Sudip Ghosh ,&nbsp;Venkata Ramana Yagnambhatt","doi":"10.1016/j.genrep.2024.102033","DOIUrl":"10.1016/j.genrep.2024.102033","url":null,"abstract":"<div><div>Vitamin D deficiency can negatively impact the health and training efficiency of athletes. The rs10741657(G) allele in CYP2R1 gene has been associated with lower vitamin D status, potentially contributing to vitamin D deficiency observed across various populations, including Indians. This study aimed to investigate whether the CYP2R1 (rs10741657) polymorphism is contributing to the vitamin D status among Indian athletes. Blood samples were collected from 92 Indian elite and sub-elite athletes participating in weightlifting (29), badminton (32), athletics (14), and rowing (17) for laboratory analysis. PCR-RFLP of the CYP2R1 (rs10741657) SNP was performed, and vitamin D levels were measured. Statistical analysis was done to assess the association between genotype and vitamin D status. Vitamin D levels were comparable between genders but differed across sports, with indoor athletes, especially badminton players having higher levels. The AA genotype was associated with higher vitamin D levels compared to the GG and AG genotypes. Vitamin D deficiency is highly prevalent among the athletes studied. This deficiency may be due to the higher prevalence of the alternate allele (G) of CYP2R1 polymorphism, suggesting that genetic predisposition plays a key role in determining the vitamin D status of athletes.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102033"},"PeriodicalIF":1.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310966","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
Exploring herbal preconditioning strategies to improve adipose tissue stem cell therapy efficacy 探索提高脂肪组织干细胞疗效的草药预处理策略
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-13 DOI: 10.1016/j.genrep.2024.102030
Mahintaj Dara , Zeynab Zare-Moayedi , Yaghoob Taheri , Romina Tanideh , Shahrokh Zare , Farshid Kafilzadeh
<div><div>The application of mesenchymal stem cells (MSCs), specifically those sourced from adipose tissue, has become a focal point in regenerative medicine, showing potential for effective cell therapy. Adipose-derived stem cells (ASCs) offer hope in treating various conditions, yet their viability and integration rates are hindered by the harsh post-transplantation environment marked by inflammation and oxidative stress at the injury site. <em>Lawsonia inermis</em> (henna), <em>Zizyphus spina-christ</em>i (Christ's Thorn), and <em>Glycyrrhiza glabra</em> (licorice) are three plants known for their potent antioxidant properties primarily due to their rich content of phenolic compounds and flavonoids. Their potential health benefits make them valuable in both traditional medicine and modern therapeutic applications.</div><div>This research delves into investigating and contrasting the effects of hydroalcoholic extracts from <em>Lawsonia inermis</em>, <em>Zizyphus spina-christi</em>, and <em>Glycyrrhiza glabra</em> on human adipose tissue stem cells as a pre-conditioning method to alleviate oxidative stress in cell therapy. ASCs were isolated from the pelvic cavity and abdomen, characterized using flow cytometry, and prompted to differentiate into adipogenic and osteogenic lineages. They were then subjected to different concentrations of the aforementioned herbal extracts at varying time frames, followed by MIC and MTT analysis. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and the Minimum Inhibitory Concentration (MIC) assay are both used to evaluate the effects of substances on cell viability and cell growth receptively. RNA extraction from ASCs and evaluation of antioxidant gene expression were conducted via Real-time PCR. Flow cytometry data confirmed the presence of MSC markers in the isolated cells from ASCs. Analysis of the herbal extract concentrations revealed that 50 ng/ml had a toxic effect on ASCs, establishing a toxicity reference point for adipose-derived MSCs. Real-time PCR results showcased a notable increase in the expression of antioxidant genes post-preconditioning with hydroalcoholic extracts. This study underscores, for the first time, the safety and lack of toxicity of preconditioning with these extracts for h.ASCs, enhancing their resilience and acclimatization under oxidative stress conditions, potentially boosting the therapeutic potential of h.ASCs. The antioxidant properties of <em>Lawsonia inermis</em>, <em>Zizyphus spina-christi</em>, and <em>Glycyrrhiza glabra</em> may enhance the expression of antioxidant genes (Sod, Gpx and Cata) through several mechanisms, including the activation of transcription factors like Nrf2 (Nuclear factor erythroid 2-related factor 2), which regulates antioxidant gene expression; modulation of signaling pathways such as MAPK (Mitogen-Activated Protein Kinase) and PI3K/Akt (Phosphoinositide 3-kinase/Protein Kinase B); and influencing epigenetic modifications
间充质干细胞(MSCs),特别是来自脂肪组织的间充质干细胞的应用已成为再生医学的焦点,显示出有效细胞疗法的潜力。脂肪来源的干细胞(ASCs)为治疗各种疾病带来了希望,但其存活率和整合率却受到移植后以损伤部位的炎症和氧化应激为特征的恶劣环境的阻碍。鸡血藤、刺五加和甘草这三种植物因富含酚类化合物和类黄酮而具有强大的抗氧化功能。本研究深入研究并对比了从真皮劳桑、紫草和甘草中提取的水醇提取物对人类脂肪组织干细胞的影响,并将其作为一种预处理方法,以减轻细胞疗法中的氧化应激。从盆腔和腹部分离出 ASCs,使用流式细胞术对其进行鉴定,并促使其分化为成脂系和成骨系。然后将它们置于不同浓度、不同时间段的上述草药提取物中,再进行 MIC 和 MTT 分析。MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide)测定法和最小抑制浓度(MIC)测定法均用于评估物质对细胞活力和细胞生长接受性的影响。从 ASCs 提取 RNA 并通过实时 PCR 评估抗氧化基因的表达。流式细胞仪数据证实了从 ASCs 分离的细胞中存在间充质干细胞标记。对草药提取物浓度的分析表明,50 纳克/毫升的草药提取物对间叶干细胞有毒性作用,从而确定了脂肪来源间叶干细胞的毒性参考点。实时 PCR 结果显示,使用水醇提取物进行预处理后,抗氧化基因的表达明显增加。这项研究首次强调了用这些提取物对h.ASCs进行预处理的安全性和无毒性,增强了它们在氧化应激条件下的恢复能力和适应能力,从而有可能提高h.ASCs的治疗潜力。茵陈、紫草和甘草的抗氧化特性可通过多种机制提高抗氧化基因(Sod、Gpx 和 Cata)的表达,包括激活 Nrf2(核因子红细胞 2 相关因子 2)等转录因子,从而调节抗氧化基因的表达;调节信号通路,如 MAPK(丝裂原活化蛋白激酶)和 PI3K/Akt(磷脂酰肌醇 3 激酶/蛋白激酶 B);以及影响表观遗传修饰,如组蛋白变化或 DNA 甲基化,从而改变基因表达。然而,要弄清这些植物提取物增强抗氧化基因表达的具体机制,并探索它们在防治氧化应激相关疾病方面的潜在治疗应用,还需要进一步的研究。未来的建议应考虑更多的基因调查和体内应用,以及预处理的长期影响。
{"title":"Exploring herbal preconditioning strategies to improve adipose tissue stem cell therapy efficacy","authors":"Mahintaj Dara ,&nbsp;Zeynab Zare-Moayedi ,&nbsp;Yaghoob Taheri ,&nbsp;Romina Tanideh ,&nbsp;Shahrokh Zare ,&nbsp;Farshid Kafilzadeh","doi":"10.1016/j.genrep.2024.102030","DOIUrl":"10.1016/j.genrep.2024.102030","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The application of mesenchymal stem cells (MSCs), specifically those sourced from adipose tissue, has become a focal point in regenerative medicine, showing potential for effective cell therapy. Adipose-derived stem cells (ASCs) offer hope in treating various conditions, yet their viability and integration rates are hindered by the harsh post-transplantation environment marked by inflammation and oxidative stress at the injury site. &lt;em&gt;Lawsonia inermis&lt;/em&gt; (henna), &lt;em&gt;Zizyphus spina-christ&lt;/em&gt;i (Christ's Thorn), and &lt;em&gt;Glycyrrhiza glabra&lt;/em&gt; (licorice) are three plants known for their potent antioxidant properties primarily due to their rich content of phenolic compounds and flavonoids. Their potential health benefits make them valuable in both traditional medicine and modern therapeutic applications.&lt;/div&gt;&lt;div&gt;This research delves into investigating and contrasting the effects of hydroalcoholic extracts from &lt;em&gt;Lawsonia inermis&lt;/em&gt;, &lt;em&gt;Zizyphus spina-christi&lt;/em&gt;, and &lt;em&gt;Glycyrrhiza glabra&lt;/em&gt; on human adipose tissue stem cells as a pre-conditioning method to alleviate oxidative stress in cell therapy. ASCs were isolated from the pelvic cavity and abdomen, characterized using flow cytometry, and prompted to differentiate into adipogenic and osteogenic lineages. They were then subjected to different concentrations of the aforementioned herbal extracts at varying time frames, followed by MIC and MTT analysis. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and the Minimum Inhibitory Concentration (MIC) assay are both used to evaluate the effects of substances on cell viability and cell growth receptively. RNA extraction from ASCs and evaluation of antioxidant gene expression were conducted via Real-time PCR. Flow cytometry data confirmed the presence of MSC markers in the isolated cells from ASCs. Analysis of the herbal extract concentrations revealed that 50 ng/ml had a toxic effect on ASCs, establishing a toxicity reference point for adipose-derived MSCs. Real-time PCR results showcased a notable increase in the expression of antioxidant genes post-preconditioning with hydroalcoholic extracts. This study underscores, for the first time, the safety and lack of toxicity of preconditioning with these extracts for h.ASCs, enhancing their resilience and acclimatization under oxidative stress conditions, potentially boosting the therapeutic potential of h.ASCs. The antioxidant properties of &lt;em&gt;Lawsonia inermis&lt;/em&gt;, &lt;em&gt;Zizyphus spina-christi&lt;/em&gt;, and &lt;em&gt;Glycyrrhiza glabra&lt;/em&gt; may enhance the expression of antioxidant genes (Sod, Gpx and Cata) through several mechanisms, including the activation of transcription factors like Nrf2 (Nuclear factor erythroid 2-related factor 2), which regulates antioxidant gene expression; modulation of signaling pathways such as MAPK (Mitogen-Activated Protein Kinase) and PI3K/Akt (Phosphoinositide 3-kinase/Protein Kinase B); and influencing epigenetic modifications ","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102030"},"PeriodicalIF":1.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A retrospective whole genome sequencing of SARS-CoV-2 isolate from respiratory sample of an individual from Ota – Ogun State, Nigeria 从尼日利亚奥贡州奥塔一名患者的呼吸道样本中分离出的 SARS-CoV-2 全基因组回顾性测序结果
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-13 DOI: 10.1016/j.genrep.2024.102032
Olajumoke Olufunmilayo Joseph , Samuel Olatunde Dahunsi , Anthony Okoh

Severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2) which was responsible for the COVID-19 pandemic has now been considered an endemic virus, that will continually produce sporadic outbreaks in different communities around the globe. Although, there are several surveillance studies on SARS-CoV-2 globally, including Nigeria, there is still an important need to understand the uniqueness of the strains of the virus that was circulating immediately after the pandemic, to add to the global database of information that will aid vaccine production and future preparedness against another SARS - related CoV pandemic.

Towards the end of the pandemic, between February – August 2022, SARS-CoV-2 was detected in a surveillance project in Ota – Ogun State Nigeria. We carried out a retrospective whole genome sequencing (WGS) analysis of SARS-CoV-2 in the previously reported positive sample, at Inqaba biotech in South Africa. RNA extraction was carried out using the Quick – RNA viral kit (Zymo) and library preparation was done by NEBNext ARTIC SARS-CoV-2 FS Library Prep kit (Illumina) according to the manufacturer's instruction. The WGS was carried out on the NextSeq500 platform by Illumina. The fastq file containing the unassembled raw sequence reads were submitted to NCBI SARS-CoV-2 resources, and a BioProject accession number PRJNA1076330 was issued. The DRAGEN Targeted Microbial, GISAID-CoVsurver mutation, BLAST and MAFFT applications were used for analysis.

The spike (s) gene of the study sequence possessed seven mutations (G142D, A163V, V213G, D614G, H655Y, N679K, P681H) and shared 99.4 % identity with those of the Wuhan reference sequence WIV04. The non-structural proteins (NSP) – 7,8,9,10 and 16 shared 100 % identity with bat/Yunnan/RaTG13 (a SARS- related CoV found in bats) sequence on GISAID. Although, the study sequence was obtained from an asymptomatic individual, the S mutations observed are known to be related to virulence, antigenic shift, enhanced transmissibility and host change. Thus, upon successful exploitation of this asymptomatic variant, it may possibly be transformed to a potential candidate for SARS-CoV-2 vaccine in future.

造成 COVID-19 大流行的严重急性呼吸系统综合症冠状病毒-2(SARS-CoV-2)现在已被认为是一种地方性病毒,会在全球不同的社区持续爆发。尽管包括尼日利亚在内的全球范围内对 SARS-CoV-2 进行了多项监测研究,但仍有必要了解大流行后立即流行的该病毒株的独特性,以充实全球信息数据库,从而帮助疫苗生产和未来应对另一场 SARS 相关 CoV 大流行。我们在南非 Inqaba 生物技术公司对之前报告的阳性样本中的 SARS-CoV-2 进行了回顾性全基因组测序(WGS)分析。RNA 提取使用 Quick - RNA 病毒试剂盒(Zymo),文库制备使用 NEBNext ARTIC SARS-CoV-2 FS 文库制备试剂盒(Illumina),按照制造商的说明进行。WGS 在 Illumina 的 NextSeq500 平台上进行。包含未组装原始序列读数的 fastq 文件已提交给 NCBI SARS-CoV-2 资源,并获得了 BioProject 加入号 PRJNA1076330。研究序列中的尖峰(s)基因有7个突变(G142D, A163V, V213G, D614G, H655Y, N679K, P681H),与武汉参考序列WIV04中的尖峰(s)基因有99.4%的相同性。非结构蛋白(NSP)--7、8、9、10 和 16 与 GISAID 上的蝙蝠/云南/RaTG13(一种在蝙蝠中发现的 SARS 相关 CoV)序列具有 100 % 的同一性。虽然研究序列是从一个无症状的个体身上获得的,但观察到的 S 突变与毒力、抗原转变、传播性增强和宿主改变有关。因此,在成功利用这种无症状变异体后,它有可能转变为未来 SARS-CoV-2 疫苗的潜在候选者。
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引用次数: 0
Lysine metabolism pathway as a target for drug repurposing: In silico approach against carbapenem-resistant Klebsiella pneumoniae 将赖氨酸代谢途径作为药物再利用的目标:针对耐碳青霉烯类耐药肺炎克雷伯菌的硅学方法
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-12 DOI: 10.1016/j.genrep.2024.102028
Faiza Jamil , Kanwal Khan , Noor ul Ain Zahra , Reaz Uddin
Klebsiella pneumoniae (Kp) is a pathogenic bacterium known for its capacity to induce severe infections in humans, posing a significant threat to public health. Its resistance profile, particularly against carbapenem antibiotics, presents formidable challenges in clinical management. In response, a research endeavor was undertaken to discern prospective therapeutic targets against this pathogen. The investigation focused on delineating pivotal proteins involved in Host-Pathogen Interactions (HPIs) essential for the survival of Kp, thereby serving as potential targets for drug intervention. Through a careful screening process encompassing 438 proteins, 16 candidates were identified, prioritized based on criteria such as non-homology, essentiality, and druggability. Among these, 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase (DapD), instrumental in lysine metabolism, emerged as a promising candidate for further scrutiny as a drug target against K. pneumoniae. Subsequently, employing virtual screening and molecular docking techniques, the study evaluated the 9214-compound FDA library to pinpoint potential drug candidates targeting the DapD protein. Ultimately, 15 compounds exhibiting promise were identified, suggesting the prospect of repurposing these agents for the treatment of Kp infections. This research delineates a promising step in the quest for novel therapeutics against K. pneumoniae, signifying a potential paradigm shift in combating this resilient bacterial strain. The findings hold promise for the development of more efficacious and safer antimicrobial agents, thereby addressing the pressing clinical need posed by antibiotic-resistant pathogens.
肺炎克雷伯氏菌(Kp)是一种病原菌,因其能诱发人类严重感染而闻名,对公共卫生构成重大威胁。它的耐药性,尤其是对碳青霉烯类抗生素的耐药性,给临床治疗带来了巨大挑战。为此,我们开展了一项研究工作,以确定针对这种病原体的潜在治疗目标。研究重点是确定参与宿主-病原体相互作用(HPIs)的关键蛋白,这些蛋白对 Kp 的生存至关重要,因此可作为药物干预的潜在靶点。通过对 438 个蛋白质的仔细筛选,确定了 16 个候选蛋白质,并根据非同源性、必需性和可药用性等标准进行了优先排序。其中,2,3,4,5-四氢吡啶-2,6-二羧酸 N-琥珀酰基转移酶(DapD)在赖氨酸代谢中起着重要作用,它有望成为肺炎克氏菌的药物靶点,需要进一步研究。随后,该研究采用虚拟筛选和分子对接技术,对包含 9214 种化合物的 FDA 文库进行了评估,以确定针对 DapD 蛋白的潜在候选药物。最终,确定了 15 种有前景的化合物,表明这些药物有望重新用于治疗 Kp 感染。这项研究为寻找针对肺炎克氏菌的新型疗法迈出了充满希望的一步,标志着抗击这种顽强细菌菌株的模式可能发生转变。研究结果有望开发出更有效、更安全的抗菌药物,从而解决抗生素耐药病原体带来的迫切临床需求。
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引用次数: 0
Relation of rs846910, rs4844880 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) polymorphisms with the risk of preeclampsia: A case-control study rs846910、rs4844880 11β-羟类固醇脱氢酶 1 型 (HSD11B1) 多态性与子痫前期风险的关系:一项病例对照研究
IF 1 Q4 GENETICS & HEREDITY Pub Date : 2024-09-12 DOI: 10.1016/j.genrep.2024.102026
Hedia Zitouni , Vera Chayeb , Nozha Raguema , Marwa Ben Ali Gannoun , Touhami Mahjoub , Jean Guibourdenche , Wassim Y. Almawi

Background

The 11β-hydroxysteroid-dehydrogenase 1 (11β-HSD1) enzyme catalyzes the interconversion of cortisone and cortisol, with mainly oxoreductive activity in intact cells due to co-expression with hexose-6-phosphate dehydrogenase (H6PD). The uterine localization of 11β-HSD1 and its reduced placental expression in women with preeclampsia (PE) suggest a role for 11β-HSD1 in PE pathogenesis. We investigated the association of rs4844880 and rs846910 variants in the HSD11B1 gene with PE in Tunisian women.

Methods

The study cases comprised 334 women who presented with PE and 314 age-matched normotensive women who served as controls. The rs4844880 and rs846910 HSD11B1 gene variants were genotyped by real-time PCR.

Results

The rs4844880 T > A and rs846910 G > A minor allele frequencies were not different between PE cases and control women, which persisted after adjusting for age, BMI, gestational age, premature delivery, and baby weight. An association was noted for rs4844880 A/A genotype with a heightened risk of PE, which persisted after controlling key covariates. The (minor) A allele of rs4844880 was linked with elevated serum ALT and higher serum AST. In contrast, carriage of the rs846910 minor (A) allele was connected with higher baby weight on delivery and serum AST levels. Setting the major allele homozygotes (T-G) as a reference, a higher prevalence of double minor allele (A-A) haplotype was seen in PE cases than in corresponding controls, which persisted after controlling for age and BMI. Controlling for gestational age and baby weight identified the T-A haplotype and confirmed the association of the A-A haplotype with a heightened risk of PE.

Conclusion

Our results support an association between HSD11B1 polymorphisms and increased risk of PE and PE-associated clinical features.

背景11β-羟类固醇脱氢酶1(11β-HSD1)催化可的松和皮质醇的相互转化,由于与己糖-6-磷酸脱氢酶(H6PD)共同表达,在完整细胞中主要具有氧化还原活性。11β-HSD1 的子宫定位及其在子痫前期(PE)妇女胎盘中的表达减少表明,11β-HSD1 在子痫前期发病机制中发挥作用。我们研究了突尼斯妇女 HSD11B1 基因中 rs4844880 和 rs846910 变体与 PE 的关系。rs4844880和rs846910 HSD11B1基因变异通过实时PCR进行基因分型。结果rs4844880 T >A和rs846910 G >A小等位基因频率在PE病例和对照组妇女之间没有差异,在调整了年龄、体重指数、胎龄、早产和婴儿体重后,差异依然存在。rs4844880的A/A基因型与PE风险升高有关,在控制了关键的协变量后,这种关系依然存在。rs4844880 的(次要)A 等位基因与血清谷丙转氨酶升高和血清谷草转氨酶升高有关。相反,携带 rs846910 小(A)等位基因与婴儿出生时体重增加和血清 AST 水平升高有关。以主要等位基因的同源染色体(T-G)为参照,PE 病例中双次要等位基因(A-A)单倍型的发生率高于相应的对照组,在控制了年龄和体重指数后,这种情况依然存在。结论:我们的研究结果支持 HSD11B1 多态性与 PE 风险增加及 PE 相关临床特征之间存在关联。
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Gene Reports
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