Gene Reports最新文献

Genetic expression in cancer research: Challenges and complexity 癌症研究中的基因表达：挑战与复杂性

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-21 DOI: 10.1016/j.genrep.2024.102042

Cancer research is profoundly influenced by the complex interplay of gene expression, yet conventional studies often emphasize genes with high expression levels, potentially overlooking those that contribute subtly to tumorigenesis. This review challenges the standard paradigms by questioning the direct causality often attributed to high gene expression in cancer progression and underscores the importance of distinguishing correlation from causation. It highlights how traditional bulk data analysis might mask crucial cell-specific gene activities, a limitation increasingly addressed by emerging single-cell and spatial transcriptomics, albeit with their own inherent challenges. Additionally, the review delves into the critical roles of both oncogenes and tumor driver genes, advocating for a precise differentiation in research and therapy. Furthermore, it discusses the revolutionary impact of CRISPR technology in identifying essential genes for cancer cell survival, which, while crucial, may not necessarily drive cancer. The complexities of epigenetic regulation and the discrepancies between mRNA and protein expression levels are also explored, emphasizing the necessity for integrated approaches that combine transcriptomics, proteomics, and computational models. This integrated perspective is vital for developing targeted therapies that address the multifaceted nature of gene expression and its regulation in cancer, aiming to refine therapeutic strategies and enhance clinical outcomes.

癌症研究受到基因表达复杂相互作用的深刻影响，然而传统研究往往强调高表达水平的基因，却有可能忽略那些对肿瘤发生有微妙作用的基因。这篇综述挑战了标准范式，质疑了高基因表达在癌症进展中通常被归因于直接因果关系的说法，并强调了区分相关性和因果关系的重要性。它强调了传统的批量数据分析如何可能掩盖关键的细胞特异性基因活动，而新兴的单细胞和空间转录组学越来越多地解决了这一局限性，尽管它们也有其固有的挑战。此外，综述还深入探讨了致癌基因和肿瘤驱动基因的关键作用，主张在研究和治疗中进行精确区分。此外，综述还讨论了 CRISPR 技术在确定癌细胞存活的关键基因方面的革命性影响，这些基因虽然至关重要，但不一定会导致癌症。报告还探讨了表观遗传调控的复杂性以及 mRNA 和蛋白质表达水平之间的差异，强调了结合转录组学、蛋白质组学和计算模型的综合方法的必要性。这种综合视角对于开发靶向疗法至关重要，可解决癌症中基因表达及其调控的多面性问题，从而完善治疗策略，提高临床疗效。

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引用次数: 0

miR-16-5p may modulate migration and proliferation through TP53 and LncRNA-NEAT1 in triple-negative breast cancer miR-16-5p 可通过 TP53 和 LncRNA-NEAT1 调节三阴性乳腺癌的迁移和增殖

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-20 DOI: 10.1016/j.genrep.2024.102038

Introduction

MicroRNAs (miRNAs) are potential candidate clinical biomarkers for many diseases. This study explored the role and potential mechanisms of miR-16-5p in triple-negative breast cancer (TNBC).

Results

The expression of miR-16-5p was lower in wax block sections obtained from 47 TNBC patient samples. Overexpression of miR-16-5p decreased the migratory abilities and the cell proliferation in MDA-MB-231 cells. We found miR-16-5p modulated TP53 and LncRNA-NEAT1 in bioinformatics analysis. In transfection experiments, the higher expression of lncRNA-NEAT1 and TP53 were observed in miR-16-5p inhibitor group.

Conclusion

Our data demonstrated that miR-16-5p was lowly expressed and acted as a tumor suppressor in TNBC. Moreover, miR-16-5p regulated TNBC cell proliferation and migratory capacity by modulating TP53 and lncRNA-NEAT1 in vitro.

导言微小RNA（miRNA）是许多疾病潜在的候选临床生物标记物。本研究探讨了 miR-16-5p 在三阴性乳腺癌（TNBC）中的作用和潜在机制。过表达 miR-16-5p 会降低 MDA-MB-231 细胞的迁移能力和细胞增殖。我们在生物信息学分析中发现，miR-16-5p 可调节 TP53 和 LncRNA-NEAT1。结论我们的数据表明，miR-16-5p 在 TNBC 中低表达，并作为肿瘤抑制因子发挥作用。此外，miR-16-5p 在体外通过调节 TP53 和 lncRNA-NEAT1 来调控 TNBC 细胞的增殖和迁移能力。

引用次数: 0

miR-98 and miR-629 can be used as a potential biomarker on relapsing-remitting multiple sclerosis patients miR-98 和 miR-629 可用作复发缓解型多发性硬化症患者的潜在生物标记物

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-19 DOI: 10.1016/j.genrep.2024.102041

Introduction

Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), characterized by chronic inflammation, demyelination, and neurodegeneration. In recent years, among non-coding RNAs miRNA have emerged as key regulators of different biological processes and it has been suggested that they play an important role in the mechanisms underlying MS pathogenesis. Through in silico methods, miR-629-5p and miR-98-5p were identified as significant factors in MS pathology. The aim of this study was to examine the levels of expression of miR-629-5p and miR-98-5p in blood samples obtained from patients with relapsing–remitting MS. Methods: Total blood were recruited from RRMS and control group and qPCR analysis was used for evaluating of target miRNAs expression. The mirDIP database was utilized to identify the target genes. Hub genes were identified with the Cytoscape and target pathways were identified using the STRING. Results: Expression analysis revealed a significant upregulation of miR-629-5p and miR-98-5p (FC ≥ 1.5 and p < 0.05) in patients with RRMS. PI3K-Akt, Rap1, MAPK and FoxO signaling pathways were found as target. Discussion: The discovery of these miRNAs suggests that they may have a notable impact on MS patients by intervening on pathways involved in both the immune and nervous systems.

导言多发性硬化症（MS）是一种影响中枢神经系统（CNS）的自身免疫性疾病，以慢性炎症、脱髓鞘和神经变性为特征。近年来，在非编码 RNA 中，miRNA 已成为不同生物过程的关键调控因子，并被认为在多发性硬化症的发病机制中发挥着重要作用。通过硅学方法，miR-629-5p 和 miR-98-5p 被确定为多发性硬化症病理的重要因素。本研究旨在检测复发性多发性硬化症患者血液样本中 miR-629-5p 和 miR-98-5p 的表达水平。研究方法采集 RRMS 组和对照组患者的总血样，采用 qPCR 分析评估目标 miRNAs 的表达。利用 mirDIP 数据库确定靶基因。利用 Cytoscape 确定枢纽基因，利用 STRING 确定目标通路。结果显示表达分析表明，在 RRMS 患者中，miR-629-5p 和 miR-98-5p 表达明显上调（FC ≥ 1.5，p < 0.05）。PI3K-Akt、Rap1、MAPK和FoxO信号通路被认为是靶点。讨论这些 miRNAs 的发现表明，它们可能通过干预免疫系统和神经系统的通路对多发性硬化症患者产生显著影响。

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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

Gene Reports

Pub Date : 2024-09-18 DOI: 10.1016/j.genrep.2024.102039

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

Gene Reports

Pub Date : 2024-09-16 DOI: 10.1016/j.genrep.2024.102034

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

Gene Reports

Pub Date : 2024-09-16 DOI: 10.1016/j.genrep.2024.102035

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":"","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> < 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":null,"pages":null},"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

Gene Reports

Pub Date : 2024-09-15 DOI: 10.1016/j.genrep.2024.102027

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

Gene Reports

Pub Date : 2024-09-15 DOI: 10.1016/j.genrep.2024.102033

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。

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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

Gene Reports

Pub Date : 2024-09-13 DOI: 10.1016/j.genrep.2024.102030

<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":"","doi":"10.1016/j.genrep.2024.102030","DOIUrl":"10.1016/j.genrep.2024.102030","url":null,"abstract":"<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 ","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":null,"pages":null},"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

Gene Reports

Pub Date : 2024-09-13 DOI: 10.1016/j.genrep.2024.102032

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