Gene Reports最新文献_第5页

Impact of genetic variants TLR2 rs5743708 and rs3804099 on the susceptibility of individuals to severe coronavirus disease 2019 基因变异TLR2 rs5743708和rs3804099对个体对2019年严重冠状病毒病易感性的影响

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-20 DOI: 10.1016/j.genrep.2025.102384

Maryam Noroozi , Kamran Heidarnejad , Reza Shafiei , Reza Shahbazi , Kurosh Kalantar , Mona Fani

Background

Pattern recognition receptors (PRRs) of the innate immune system potentially detect pathogen-associated molecular patterns (PAMPs) following viral invasion. While some Toll-like receptors (TLRs) offer protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, various studies suggest that Toll-like Receptor 2 (TLR2) activity is linked to heightened inflammatory responses and severe disease outcomes.

Methods

This study investigated two TLR2 single-nucleotide polymorphisms (SNPs), rs5743708 and rs3804099, using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) in patients with mild and severe COVID-19.

Results

Genotypic and allelic analyses revealed no statistically significant differences between severity groups. However, rs3804099 showed a significant association with creatinine and sodium levels in severe COVID-19 patients—creatinine differed between CT and TT genotypes, and sodium between CT and CC genotypes. Previous evidence associates this polymorphism with proteinuria after kidney transplantation, suggesting a role in renal homeostasis.

Conclusion

Our findings raise the possibility that rs3804099 may serve as a genetic marker for susceptibility to renal dysfunction and electrolyte imbalance during COVID-19, extending the clinical relevance of TLR2 polymorphisms beyond inflammatory signaling.

先天免疫系统的模式识别受体（PRRs）可能在病毒入侵后检测病原体相关的分子模式（PAMPs）。虽然一些toll样受体（TLRs）可以预防严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染，但各种研究表明，toll样受体2 （TLR2）活性与炎症反应加剧和严重疾病结局有关。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对轻、重度COVID-19患者的TLR2单核苷酸多态性rss5743708和rs3804099进行检测。结果基因型分析和等位基因分析显示，严重程度组间差异无统计学意义。然而，rs3804099与COVID-19重症患者的肌酐和钠水平有显著相关性——CT和TT基因型之间的肌酐水平存在差异，CT和CC基因型之间的钠水平存在差异。先前的证据表明，这种多态性与肾移植后的蛋白尿有关，表明它在肾脏稳态中起作用。结论rs3804099可能作为COVID-19患者肾功能障碍和电解质失衡易感性的遗传标记，将TLR2多态性的临床意义扩展到炎症信号之外。

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引用次数: 0

Acquisition of multiple drug resistance genes by a novel isolate of A. junii from plastic laden landfill soil through horizontal gene transfer 从垃圾填埋场填满塑料的土壤中通过水平基因转移获得一株新菌株的多重耐药基因

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-19 DOI: 10.1016/j.genrep.2025.102387

Kaustubh Jumle , Naveen Malik , Sudarshan Singh Lakhawat , Baljinder Singh , Himanshu Gogoi , Akhilesh Kumar , Pushpender Kumar Sharma

In the present study, we have investigated and compared metagenome sample of plastic-laden landfill soil with garden soil for the presence of antimicrobial resistance (AMR) genes. Interestingly, during the analysis, we identified several AMR genes that include sul1and sul2 encoding sulfonamide resistance, emr (A) and emr (33) encoding macrolide resistance, bla AQU-3 coding β lactam resistance, vanX (A) coding glycopeptide resistance and drfG coding diaminopyrimidine resistance in plastic-laden landfill soil, whereas no AMR genes could be annotated in the garden soil metagenome sample. Furthermore, screening of AMR phenotype from a plastic-laden landfill soil reveals a bacterium demonstrating resistance to different classes of antibiotics. The whole genome sequencing and analysis reveals its close similarity with Acinetobacter junii, the strain identified henceforth named A. junii JPR0524. Assembled genome demonstrated ∼40 % GC content, and a genome size of ∼3.5 Mbp. Interestingly, several AMR genes could be annotated in A. junii JPR0524 genome. We also predicted several horizontal gene transfer (HGT) sites in JPR0524 genome, noticeably many of these sites overlapped with the predicted AMR genes sites. In addition, insertion of phage DNA fragments was also predicted at one end of the assembled genome, presumably attributed to horizontal gene transfer. Altogether, it appears that strain A. junii JPR0524 might have acquired these multidrug resistance genes in landfill sites through the horizontal gene transfer as evident from identification of putative HGT site in its genome.

在本研究中，我们调查并比较了垃圾填埋场土壤和花园土壤的宏基因组样本中抗菌素耐药性（AMR）基因的存在。有趣的是，在分析过程中，我们发现了几个AMR基因，包括编码磺胺抗性的sul1和sul2，编码大环内酯抗性的emr (A)和emr(33)，编码β内酰胺抗性的bla aqu3，编码糖肽抗性的vanX (A)和编码二氨基嘧啶抗性的drfG，而在花园土壤宏基因组样本中没有AMR基因被注释。此外，从充满塑料的垃圾填埋场土壤中筛选AMR表型揭示了一种细菌对不同类别的抗生素表现出耐药性。全基因组测序和分析结果表明，该菌株与朱尼不动杆菌（a.j junii JPR0524）具有密切的相似性。组装的基因组显示出约40%的GC含量，基因组大小约为3.5 Mbp。有趣的是，几个AMR基因可以在刺桐JPR0524基因组中被注释。我们还预测了JPR0524基因组中的几个水平基因转移（HGT）位点，值得注意的是，这些位点中有许多与预测的AMR基因位点重叠。此外，噬菌体DNA片段的插入也被预测在组装基因组的一端，可能归因于水平基因转移。总之，juni菌株JPR0524可能通过水平基因转移在垃圾填埋场获得了这些多药耐药基因，这一点从其基因组中推定的HGT位点的鉴定中得到了证明。

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引用次数: 0

Genomic characterization and bioactive potential of a Kitasatospora sp. from the rhizosphere of Inga edulis 印加根际一株Kitasatospora sp.的基因组特征及其生物活性潜力

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-14 DOI: 10.1016/j.genrep.2025.102381

Rafael de Souza Rodrigues , Antonia Queiroz Lima de Souza , Jania Lilia da Silva Bentes , Elison de Souza Sevalho , Kamila Rangel Primo Fernandes , Anderson Nogueira Barbosa , Maria de Fátima Oliveira Almeida , Rafael Pinto e Souza , Roneres Deniz Barbosa , Jeferson Chagas da Cruz , Ivanildes dos Santos Bastos , Patrícia Puccinelli Orlandi , Gilvan Ferreira da Silva , Afonso Duarte Leão de Souza

The genus Kitasatospora (phylum Actinobacteria) includes over 44 recognized species, yet their potential to produce bioactive compounds remains largely unexplored. In this study, we report the isolation and characterization of Kitasatospora sp. LaBMicrA B282, demonstrating its distinctiveness as an actinomycete associated with the rhizosphere of Inga edulis in an Amazonian urban forest fragment. The strain is Gram-positive, aerobic, and forms brownish-white aerial and grayish-brown substrate mycelia on ISP2+starch medium. The BLAST analysis of the 16S rRNA gene (<99 %% identity) and low genomic relatedness (ANI: 82.86–83.42 %; dDDH2: 27.20–29.60 %; dDDH4: 27.1–27.2 %) support its classification as a distinct species within the genus. Genome mining via antiSMASH identified 63 putative biosynthetic gene clusters (BGCs), including clusters with 100 % similarity to those for geosmin, 2-methylisoborneol, and ε-poly-l-lysine. Bioactivity assays revealed that the aqueous supernatant fraction displayed antiplasmodial activity against Plasmodium falciparum W2 (IC₅₀ = 36.10 μg/mL), while the AcOEt/2-propanol fraction showed fungicidal activity against four pathogenic fungi. These results highlight the remarkable biosynthetic and therapeutic potential of Kitasatospora strains from underexplored environments. Our findings emphasize the importance of investigating microbial diversity in unique ecological niches like the Amazonian rhizosphere and reinforce the need to conserve these environments as reservoirs of novel bioactive compounds.

Kitasatospora属（放线菌门）包括超过44个已知的物种，但它们产生生物活性化合物的潜力在很大程度上仍未被开发。在这项研究中，我们报道了Kitasatospora sp. LaBMicrA B282的分离和鉴定，证明了它作为亚马逊城市森林片段中Inga edulis根际相关的放线菌的独特性。菌株为革兰氏阳性，需氧，在ISP2+淀粉培养基上形成褐白色和灰褐色的底物菌丝。16S rRNA基因的BLAST分析（<； 99%的同源性）和低基因组亲缘性（ANI: 82.86 - 83.42%; dDDH2: 27.20 - 29.60%; dDDH4: 27.1 - 27.2%）支持其作为属内独特物种的分类。通过反smash进行基因组挖掘，鉴定出63个假定的生物合成基因簇（bgc），其中包括与土臭素、2-甲基异龙脑和ε-聚赖氨酸具有100%相似性的簇。生物活性测定表明，水上清部分对恶性疟原虫W2 （IC₅₀= 36.10 μg/mL）具有抗疟原虫活性，而AcOEt/2-丙醇部分对四种病原真菌具有杀菌活性。这些结果突出了从未开发的环境中提取的Kitasatospora菌株具有显著的生物合成和治疗潜力。我们的研究结果强调了在亚马逊根际等独特生态位中研究微生物多样性的重要性，并强调了保护这些环境作为新型生物活性化合物储存库的必要性。

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引用次数: 0

Hyperglycemia elevates oxidative stress markers without triggering mitochondrial large-scale deletions in peripheral blood leukocytes of type 2 diabetes patients 高血糖会升高2型糖尿病患者外周血白细胞的氧化应激标志物，而不会引发线粒体大规模缺失

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-14 DOI: 10.1016/j.genrep.2025.102385

Tejas Tajane , Prafulla Ambulkar , Pranita Waghmare , Bharati Taksande , Jwalant Waghmare

Objective

This study aimed to assess whether hyperglycemia-mediated reactive oxygen species (ROS) can cause a long-range deletion in the mitochondrial genome.

Methods

We assessed oxidative damage byproducts, such as 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA), in blood serum samples using the Enzyme-linked Immunosorbent Assay (ELISA) method in diabetes and healthy cohorts. In addition, the long-range mtDNA deletion (ΔmtDNA⁴⁹⁷⁷) assay was used to evaluate mtDNA deletions in peripheral blood leucocytes of type 2 diabetes patients. The Receiver Operating Characteristic (ROC) curve was computed to analyse the relationship between oxidative markers in the study groups.

Result

Serum 8-OHdG (34.44 ± 1.17 ng/mL) and MDA (65.90 ± 3.15 μmol/L) levels were significantly higher (p < 0.0001) in the diabetic group compared to the healthy controls (18.72 ± 0.71 ng/mL and 43.60 ± 2.47 μmol/L, respectively). The prevalence of hypertension also differed significantly between groups (p < 0.0001) and appeared to be positively associated with elevated 8-OHdG levels. However, ΔmtDNA⁴⁹⁷⁷ was not detected in the peripheral blood leucocytes of either study group. The ROC curve analysis indicated that 8-OHdG exhibited greater diagnostic accuracy than MDA for distinguishing diabetic patients, demonstrating higher specificity and a larger area under the curve (AUC).

Conclusion

Hyperglycemia elevated oxidative markers but failed to induce ΔmtDNA⁴⁹⁷⁷ in peripheral blood leucocytes. There was no ostensible association between ΔmtDNA⁴⁹⁷⁷ and diabetes mellitus.

目的本研究旨在评估高血糖介导的活性氧（ROS）是否会导致线粒体基因组的远程缺失。方法采用酶联免疫吸附法（ELISA）检测糖尿病和健康人群血清中氧化损伤副产物8-羟基脱氧鸟苷（8-OHdG）和丙二醛（MDA）的含量。此外，采用远程mtDNA缺失（ΔmtDNA4977）检测方法评估2型糖尿病患者外周血白细胞mtDNA缺失情况。计算受试者工作特征（ROC）曲线，分析各研究组氧化标志物之间的关系。结果糖尿病组血清8-OHdG（34.44±1.17 ng/mL）和MDA（65.90±3.15 μmol/L）水平显著高于健康对照组（18.72±0.71 ng/mL和43.60±2.47 μmol/L）（p < 0.0001）。高血压患病率在两组之间也有显著差异（p < 0.0001），并且似乎与8-OHdG水平升高呈正相关。然而，在两个研究组的外周血白细胞中均未检测到ΔmtDNA4977。ROC曲线分析表明，8-OHdG对糖尿病患者的诊断准确率高于MDA，具有更高的特异性和更大的曲线下面积（AUC）。结论高血糖使外周血白细胞氧化标志物升高，但对ΔmtDNA4977无诱导作用。ΔmtDNA4977与糖尿病之间没有明显的联系。

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引用次数: 0

Zinc oxide nanoparticle conjugated with Lapatinib has apoptogenic effect on colon cancer cell line 氧化锌纳米颗粒结合拉帕替尼对结肠癌细胞系有凋亡作用

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-13 DOI: 10.1016/j.genrep.2025.102383

Seyed Milad Mousavi Eshkelani , Riham Nasser , Fatemeh Ghaderibarmi , Fatemeh Mirzaee , Farideh Tahmoresi , Arash Davoudi , Hedyeh Bagheri Darestani , Nafiseh Khakzad , Diba Heidari , Sana Tarashandeh Hemmati , Shahrzad Aghajani , Taraneh Ghasemipour , Fahimeh Abedini Bajgiran , Ahmed Raheem Rayshan , Ali salehzadeh

Adjuvant chemotherapy for colon cancer in its advanced stages is not associated with much success. Nanoparticle-mediated delivery of anticancer drugs represents an innovative approach for efficient and specific targeting of cancer cells. In this work, ZnO NPs were functionalized with glucose and conjugated with Lapatinib. Next, their anticancer effects on colon cancer cells were investigated. Physicochemical properties of ZnO@Glu-Lapatinib NPs were analyzed by FT-IR, XRD, EDS, DLS, Zeta potential measurement, and SEM and TEM microscopy. Cell viability in the colon cancer (SW480) and normal (HEK293) cells treated with the NPs was determined and 50 % inhibitory concentration (IC₅₀) was calculated. Cell cycle and apoptosis/necrosis analyses in the cancer cells were performed by flow cytometry and the expression level of the CASP8 and CASP9 genes was investigated by real-time PCR. Hoechst staining was performed to see the morphology of apoptotic cells. The ZnO@Glu-Lapatinib NPs were correctly synthesized with a spherical shape, DLS of 872.4 nm, zeta potential of −39.2, without impurity and diameter of 43.7–63.8 nm in their dry form. The IC₅₀ of ZnO@Glu-Lapatinib NPs in the normal and cancer cell lines were 36.82 and 7.78 μg/mL, respectively. Treatment of cancer cells with ZnO@Glu-Lapatinib NPs increased cell apoptosis, mainly early apoptosis (74.3 %) and elevated cell cycle blockage at the G0/G1 phase (79.9 %). Alterations in nuclear morphology such as chromatin condensation and fragmentation in favor of apoptosis were evident in cancer cells treated with ZnO@Glu-Lapatinib NPs in Hoechst staining. The expression levels of the CASP8 and CASP9 in the treated cancer cells increased to 6.4 and 3.9 folds, respectively. ROS analysis showed a 50.9-fold increase in reactive oxygen species oxidative after treatment. This study exhibited that ZnO@Glu-Lapatinib is a potential anticancer candidate that reduces the viability of colon cancer cells by inducing apoptosis pathways.

晚期结肠癌的辅助化疗成功率不高。纳米颗粒介导的抗癌药物递送代表了一种有效和特异性靶向癌细胞的创新方法。在这项工作中，ZnO NPs被葡萄糖功能化并与拉帕替尼偶联。接下来，研究了它们对结肠癌细胞的抗癌作用。采用FT-IR、XRD、EDS、DLS、Zeta电位测量、SEM和TEM显微镜对ZnO@Glu-Lapatinib NPs的理化性质进行了分析。测定NPs作用于结肠癌（SW480）和正常（HEK293）细胞的细胞活力，并计算50%抑制浓度（IC50）。流式细胞术检测肿瘤细胞周期和凋亡/坏死，实时荧光定量PCR检测CASP8和CASP9基因的表达水平。采用Hoechst染色观察凋亡细胞形态。合成的ZnO@Glu-Lapatinib纳米粒子为球形，DLS为872.4 nm， zeta电位为- 39.2，无杂质，干态直径为43.7 ~ 63.8 nm。ZnO@Glu-Lapatinib NPs在正常和肿瘤细胞株中的IC50分别为36.82和7.78 μg/mL。ZnO@Glu-Lapatinib NPs治疗癌细胞增加了细胞凋亡，主要是早期凋亡（74.3%）和G0/G1期细胞周期阻滞（79.9%）。Hoechst染色显示，在ZnO@Glu-Lapatinib NPs处理的癌细胞中，核形态的改变，如染色质凝聚和碎片化，有利于细胞凋亡。CASP8和CASP9在处理后的癌细胞中的表达水平分别增加到6.4倍和3.9倍。活性氧分析显示，处理后活性氧增加50.9倍。该研究表明ZnO@Glu-Lapatinib是一种潜在的抗癌候选者，通过诱导凋亡途径降低结肠癌细胞的活力。

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引用次数: 0

Deciphering functional genes and pathways associated with enzyme activity during fruiting development of Tremella fuciformis and Annulohypoxylon stygium 银耳和木耳果实发育过程中酶活性相关功能基因和途径的解读

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-12 DOI: 10.1016/j.genrep.2025.102382

Jia-Li Shi , Yong-Qiang Hu , Jian-Qiang Ye , Xu-Zhou Liu , Shi-Yan Wei , Li-Ying Li , Ming-Guo Jiang , Liang-Liang Qi

Tremella fuciformis relies on the nutrient supply from its host fungus Annulohypoxylon stygium during development, but the molecular basis of enzyme activity in their interaction remains unclear. Here, we measured the activities of cellulase, neutral xylanase, amylase, neutral protease, and chitinase during the fruiting process. Enzyme activities showed dynamic changes, with consistently higher levels in mixed mycelium than in A. stygium mycelium. To explore the underlying basis, transcriptome analyses were conducted at three stages, detecting 2533, 2276, and 1326 differentially expressed genes (DEGs) in BHy_14 vs AHy_14, BHy_21 vs AHy_21, and BHy_28 vs AHy_28, respectively (BHy represents the mixed mycelia of T. fuciformis and A. stygium, while AHy represents the mycelia of A. stygium alone; 14, 21, and 28 represent the 14th, 21st, and 28th days of cultivation, respectively). GO and KEGG enrichment indicated that DEGs were mainly enriched in carbohydrate and amino acid metabolism pathways. Notably, the largest number of upregulated genes occurred at 21 d, suggesting this as a key stage of metabolic regulation. Ten candidate DEGs from the BHy_21 vs AHy_21 comparison were validated by qRT-PCR, showing expression patterns consistent with the transcriptome data. Overall, this study reveals the pivotal roles of carbohydrate and amino acid metabolism in T. fuciformis–A. stygium interaction, providing molecular insights into developmental regulation and cultivation improvement.

银耳在发育过程中依赖于宿主真菌的营养供给，但二者相互作用中酶活性的分子基础尚不清楚。在此，我们测定了纤维素酶、中性木聚糖酶、淀粉酶、中性蛋白酶和几丁质酶在结果子过程中的活性。酶活性呈动态变化，混合菌丝体的酶活性始终高于混合菌丝体。为了探究其潜在的基础，我们分三个阶段进行转录组分析，分别在BHy_14与AHy_14、BHy_21与AHy_21、BHy_28与AHy_28中检测到2533、2276和1326个差异表达基因（BHy代表T. fuciformis和a.s hegium的混合菌丝，AHy代表a.s hegium的单独菌丝；14,21和28分别代表培养的第14、21和28天）。GO和KEGG富集表明DEGs主要富集于碳水化合物和氨基酸代谢途径。值得注意的是，21 d时出现最多的上调基因，这表明这是代谢调节的关键阶段。通过qRT-PCR验证了BHy_21与AHy_21比较中的10个候选deg，显示出与转录组数据一致的表达模式。总的来说，本研究揭示了碳水化合物和氨基酸代谢在T. fuciformis-A中的关键作用。Stygium相互作用，为发育调控和培养改进提供分子见解。

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引用次数: 0

Therapeutic potential of cinnamaldehyde in melanoma: An in silico and in vitro analysis of stratifin and DNMT expression 肉桂醛在黑色素瘤中的治疗潜力：层析芬和DNMT表达的计算机和体外分析

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-11 DOI: 10.1016/j.genrep.2025.102380

Ali Afgar , Reza Vahidi , Mehrnaz Sadat Ravari , Maryam Samareh Salavatipour , Fatemeh Sharifi , Mahla Sattarzadeh Bardsiri , Mostafa Amopour Bahnamiry , Hoda Ebrahimi , Marzie Ghanbarian , Mohammad-Javad Sanaei

The improper expression of DNA methyltransferase (DNMTs) genes could affect various regions of tumor suppressor genes. MicroRNAs target the DNMTs and modulate gene expression of tumor suppressor genes like stratifin. Cinnamaldehyde is also a methylation modulator with anti-cancer properties. The study predicted the miRNA targeting DNMT3A, 3B, and 1 and evaluated the expression of DNMTs, stratifin, miR-548, miR-200c, miR-193a, and miR-148a-5p before and after treatment with cinnamaldehyde in A375 melanoma cell lines. MicroRNAs were predicted and selected by miRanda, miRDB, miRWalk, RNAhybrid, PICTAR4, PICTAR5, PITA, RNA22, and Targetsca. The analysis of this relationship included docking and 2D interaction plots, and the expression of stratifin, DNMTs, and miRNAs was determined by real-time PCR.

The expression of hsa-miR-548, miR-193a, and miR-148 was dramatically reduced, while the expression of hsa-miR-200c was elevated. Following treatment with Cinnamaldehyde, the results were reversed for DNMT3B and stratifin genes in melanoma compared with melanocytes. Additionally, molecular dynamics simulations showed increased RMSD and Rg values, reduced hydrogen bonding, and higher SASA following cinnamaldehyde binding to DNMT3B, supporting ligand-induced conformational shifts.

We hypothesized that abnormal microRNA expression may disrupt DNMT function by methylating stratifin, but this effect may be reversed with cinnamaldehyde treatment.

DNA甲基转移酶（DNA methyltransferase, dnmt）基因的异常表达可影响肿瘤抑制基因的多个区域。MicroRNAs以dnmt为靶点，调控肿瘤抑制基因如stratifin的基因表达。肉桂醛也是一种具有抗癌特性的甲基化调节剂。本研究预测了靶向DNMT3A、3B和1的miRNA，并评估了肉桂醛治疗A375黑色素瘤细胞系前后dnmt、stratifin、miR-548、miR-200c、miR-193a和miR-148a-5p的表达。通过miRanda、miRDB、miRWalk、RNAhybrid、PICTAR4、PICTAR5、PITA、RNA22和Targetsca预测和选择microrna。这种关系的分析包括对接和2D相互作用图，并通过实时PCR检测stratifin、dnmt和mirna的表达。hsa-miR-548、miR-193a和miR-148的表达显著降低，而hsa-miR-200c的表达升高。在肉桂醛治疗后，与黑色素细胞相比，黑色素瘤中DNMT3B和stratifin基因的结果是相反的。此外，分子动力学模拟显示，肉桂醛与DNMT3B结合后，RMSD和Rg值增加，氢键减少，SASA增加，支持配体诱导的构象转移。我们假设异常的microRNA表达可能通过甲基化stratifin破坏DNMT功能，但这种影响可能通过肉桂醛处理逆转。

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引用次数: 0

Estimating genetic basis of venous thromboembolism (VTE) risk in Indian population: A case control study 估计印度人群静脉血栓栓塞（VTE）风险的遗传基础：一项病例对照研究

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-07 DOI: 10.1016/j.genrep.2025.102379

Babita Kumari , Sunanda Arya , Rashi Khare , Iti Garg , Prince , Rajneesh Kumar Joshi , Rajiv Kumar , Swati Srivastava

Venous thromboembolism (VTE) is a potentially fatal, complex multifactorial disease involving acquired, clinical and genetic risk factors. VTE results in formation of abnormal blood clots affecting 1–3 individuals per thousand in general population. Etiology to VTE is largely attributed to presence of genetic risk factors such as increased activity of coagulation factors and decreased expression of natural anti-coagulants. In such a scenario, it becomes utmost important to have a genetic predictive tool based on which the individuals susceptible to VTE pre-disposition could be screened and prophylactic measures could be taken to mitigate morbidity and mortality. Present study screened sixteen single nucleotide polymorphism (SNP) markers in blood coagulation and anti-coagulation genes. A total of 89 VTE patients and 116 age-matched healthy controls were genotyped using TaqMan-based SNP real-time PCR assays targeting coagulation and anticoagulation pathway genes. Genotypic distribution of each SNP was compared between cases and controls using chi-square (χ²) and Student's t-tests. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to assess VTE risk. A p-value <0.05 was considered statistically significant. Genetic analysis revealed that variants in F7 (rs6046) and F13 (rs6003) were associated with increased risk of venous thromboembolism (VTE), whereas changes in F13 and F10 (rs321175) appeared protective. Among anticoagulant genes, a PLG rs4252125 variant showed strong risk association, while variations in COX2 rs5788 and COX1 rs3842788 showed protective associations. Other tested variants showed no significant association with VTE. This study identifies both novel and established SNPs associated with VTE risk in the Indian population, highlighting the importance of genetic screening for personalized risk prediction.

静脉血栓栓塞（VTE）是一种潜在致命的、复杂的多因素疾病，涉及获得性、临床和遗传危险因素。静脉血栓栓塞导致异常血凝块的形成，一般人群中每千人中有1-3人患病。静脉血栓栓塞的病因主要归因于遗传风险因素的存在，如凝血因子活性增加和天然抗凝血剂表达减少。在这种情况下，拥有一种遗传预测工具变得至关重要，基于这种工具，可以筛选易患静脉血栓栓塞的个体，并采取预防措施以降低发病率和死亡率。本研究筛选了16个凝血和抗凝基因的单核苷酸多态性（SNP）标记。采用基于taqman的针对凝血和抗凝血途径基因的SNP实时PCR方法，对89例静脉血栓栓塞患者和116例年龄匹配的健康对照进行基因分型。采用χ2和Student’st检验比较病例和对照组各SNP的基因型分布。计算95%置信区间（ci）的优势比（ORs）来评估静脉血栓栓塞风险。p值<；0.05被认为具有统计学意义。遗传分析显示，F7 （rs6046）和F13 （rs6003）的变异与静脉血栓栓塞（VTE）风险增加相关，而F13和F10 （rs321175）的变异则具有保护作用。在抗凝基因中，PLG rs4252125变异具有较强的风险相关性，而COX2 rss5788和COX1 rs3842788变异具有保护相关性。其他测试的变体显示与静脉血栓栓塞没有显著关联。本研究确定了印度人群中与静脉血栓栓塞风险相关的新的和已建立的snp，强调了遗传筛查对个性化风险预测的重要性。

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引用次数: 0

A comparative review of DNA assembly strategies: From traditional to modern DNA组装策略的比较综述：从传统到现代

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-05 DOI: 10.1016/j.genrep.2025.102376

Huynh Kim Khanh Ta , L. Minh Dang , Lan Thuy Ty Nguyen

Molecular Cloning is a cornerstone technology for amplifying, expressing, and manipulating specific DNA sequences. Traditional Restriction Enzyme Cloning (REC) methods are limited by sequence dependency and the introduction of undesirable “scar” sequences, which have driven the development of more advanced assembly strategies. In this review, we critically analyze major DNA Cloning techniques—from early methods to modern seamless assembly and in vivo systems. We delineate the fundamental differences between cloning vectors, which are primarily designed for DNA amplification and stable maintenance in host cells, and expression vectors, which incorporate regulatory elements that drive the expression of recombinant proteins or the transcription of guide RNAs (gRNAs) for cell therapy applications. We describe the mechanisms and enzymes involved in each approach and evaluate their key advantages and limitations. We emphasize the distinction between “scarred” methods (e.g., Restriction Enzyme Cloning, Gateway® Cloning) and “seamless” methods (e.g., Golden Gate Assembly, Exonuclease-based Seamless Cloning), highlighting the superior precision and multi-fragment assembly capability of seamless strategies for complex DNA Cloning projects in Synthetic Biology. Finally, we compare the trade-offs between in vitro systems, which are highly efficient but costly, and in vivo assembly approaches, which are simpler and more cost-effective but typically exhibit lower efficiency—making them suitable for self-sustained academic laboratories. We conclude that the optimal cloning strategy should be selected based on the specific requirements of the project, balancing junction type (scarred/seamless), sequence dependency, multi-fragment capability, flexibility, and cost to meet the needs of each experiment.

分子克隆是扩增、表达和操纵特定DNA序列的基础技术。传统的限制性内切酶克隆（REC）方法受到序列依赖性和引入不良“疤痕”序列的限制，这推动了更先进的组装策略的发展。在这篇综述中，我们批判性地分析了主要的DNA克隆技术-从早期的方法到现代的无缝组装和体内系统。我们描述了克隆载体和表达载体之间的根本区别，克隆载体主要用于宿主细胞中的DNA扩增和稳定维持，表达载体包含驱动重组蛋白表达或引导rna （gRNAs）转录的调控元件，用于细胞治疗应用。我们描述了每种方法中涉及的机制和酶，并评估了它们的主要优点和局限性。我们强调了“疤痕”方法（例如，限制性内切酶克隆，Gateway®克隆）和“无缝”方法（例如，金门组装，基于外切酶的无缝克隆）之间的区别，突出了无缝策略在合成生物学复杂DNA克隆项目中的优越精度和多片段组装能力。最后，我们比较了体外系统（高效但昂贵）和体内组装方法（更简单，更具成本效益，但通常表现出较低的效率）之间的权衡，使它们适合自我维持的学术实验室。我们认为，最优克隆策略应根据项目的具体要求，在连接类型（疤痕/无缝）、序列依赖性、多片段能力、灵活性和成本等方面进行权衡，以满足每个实验的需求。

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引用次数: 0

Carrier frequency of spinal muscular atrophy: a large-scale study in Iranian population 脊髓性肌萎缩症的携带者频率：伊朗人群的大规模研究

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-04 DOI: 10.1016/j.genrep.2025.102378

Shahram Savad , Mohammad-Hossein Modarressi , Mahnaz Seifi-Alan , Niusha Samadaian , Saloomeh Amidi , Mona Masoomy , Shima Norouzi , Sanaz Seifi-Alan , Alireza Ronagh , Shahab Nourian , Sarang Younesi , Mohammad Mahdi Taheri Amin , Maryam Eslami , Mostafa Iranpour , Asyeh Mohammadi , Bahar Parastooei , Mahdi Heydari , Amirreza Boroumand , Mahmoud Reza Ashrafi , Donya Jahedi , Soudeh Ghafouri-Fard

Copy number variation in the SMN1 gene is the main cause of Spinal Muscular Atrophy (SMA). We assessed the carrier frequency of SMA, which is the second most common genetic disease, in the Iranian population. This paper demonstrates the largest population including unrelated subjects and also provides an evaluation with variant analysis of SMN1 in cis. To acquire inclusive molecular data about the carrier frequency of SMA and the frequency of SMN1 polymorphisms g.27134T>G (c.*3+80T>G) among Iranian population, we analyzed data from 2157 individuals referred to the Pars-Genome and Genome-Nilou laboratories for SMA carrier detection between 2018 and 2024. A total of 2003 unrelated non-consanguineous healthy individuals were selected from 2157 individuals underwent MLPA using kit P460 or P021. We also assessed available whole exome sequencing (WES) data of another cohort of patients for the presence of the c.*3+80T>G variant in the SMN1. The results indicated that 3.5 % (n = 70) were carriers of the disease, possessing only one copy of the SMN1 gene. Totally, 89 % (n = 1783) of all participants exhibited two copies of SMN1. Among 526 cases underwent assessment by P460 kit and 2211 cases underwent WES, c.*3+80T>G variant was detected in 28 (1 %) cases. This data can be used in the genetic counseling, carrier screening, and prenatal diagnosis of SMA in Iran.

SMN1基因拷贝数变异是导致脊髓性肌萎缩症的主要原因。我们评估了SMA的携带者频率，这是伊朗人群中第二常见的遗传性疾病。本文论证了包括无亲缘关系受试者在内的最大种群，并对cis中SMN1的变异分析进行了评价。为了获得伊朗人群中SMA携带者频率和SMN1多态性G . 27134t>G （c.*3+80T>；G）频率的包容性分子数据，我们分析了Pars-Genome和Genome-Nilou实验室在2018年至2024年间提供的2157名个体的SMA携带者检测数据。使用试剂盒P460或P021，从2157例患者中选择2003例无血缘关系非近亲健康个体进行MLPA。我们还评估了另一组患者的全外显子组测序（WES）数据，以确定SMN1中存在c.*3+80T>；G变异。结果表明，3.5% （n = 70）是该病的携带者，仅具有一个拷贝的SMN1基因。总的来说，89% （n = 1783）的参与者表现出两个SMN1拷贝。在526例P460检测和2211例WES检测中，28例（1%）检测到c *3+80T>；G变异。这些数据可用于遗传咨询、携带者筛查和伊朗SMA的产前诊断。

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引用次数: 0