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Exploring the clinical and pharmacotherapeutic implications of druggable genome signaling in lung adenocarcinoma: An integrated approach with transcriptome and Mendelian randomization analysis 探索可药物基因组信号在肺腺癌中的临床和药物治疗意义:转录组和孟德尔随机化分析的综合方法
Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.meomic.2025.100053
Guanrong Li , Xiao Zhu

Background

This study aimed to improve prognostic models and therapeutic targets for lung adenocarcinoma (LUAD) and explore possible tumor microenvironmental pathways. We focused on long non-coding RNAs (lncRNAs), which have been implicated in LUAD progression.

Methods

Using data from The Cancer Genome Atlas (TCGA), we developed a prognostic model based on druggable genome-associated lncRNAs. Rigorous validation confirmed its predictive accuracy. We identified Druggable Genome-Associated LncRNAs (DrugGenoLnc) and conducted functional enrichment analysis, revealing their roles in LUAD biology. Furthermore, we conducted Mendelian randomization (MR) and Bayesian weighted Mendelian Randomization (BWMR) analysis using TwoSampleMR to explore possible lung cancer-related pathways. Our assessment of the tumor microenvironment included tumor mutational burden (TMB), the TIDE algorithm, and the “pRRophetic” R package. Additionally, we analyzed stemness indices in LUAD patients.

Results

Our lncRNA-centered prognostic model demonstrated significant value for risk stratification. Functional enrichment analysis highlighted lncRNAs’ involvement in vital biological processes. MR and BWMR analysis confirmed the inhibitory effect of the “neutrophil extracellular trap formation” pathway on NSCLC. Immunological analysis identified high-risk pathways related to immune functions, potentially enhancing immunotherapy prospects for high-risk patients. Patients with high TMB had poorer overall survival, while high-risk patients showed increased chemotherapy drug sensitivity. Lastly, mRNA stem cell index (mRNAsi) correlated with LUAD patient prognosis.

Conclusion

This study underscores DrugGenoLnc’s utility as a prognostic feature, establishes a robust prognostic model for LUAD, and offers potential for early detection markers and therapeutic target identification. Furthermore, it provides insights into the anti-tumor immune microenvironment, guiding clinical treatment strategies in LUAD.
本研究旨在完善肺腺癌(LUAD)的预后模型和治疗靶点,探索可能的肿瘤微环境通路。我们重点研究了与LUAD进展有关的长链非编码rna (lncRNAs)。方法利用癌症基因组图谱(TCGA)的数据,我们建立了一个基于可药物基因组相关lncrna的预后模型。严格的验证证实了其预测的准确性。我们鉴定了可药物化的基因组相关LncRNAs (DrugGenoLnc),并进行了功能富集分析,揭示了它们在LUAD生物学中的作用。此外,我们使用TwoSampleMR进行孟德尔随机化(MR)和贝叶斯加权孟德尔随机化(BWMR)分析,以探索可能的肺癌相关途径。我们对肿瘤微环境的评估包括肿瘤突变负荷(tumor mutational burden, TMB)、TIDE算法和“prophytic”R包。此外,我们还分析了LUAD患者的干性指标。结果以lncrna为中心的预后模型对风险分层具有重要价值。功能富集分析强调lncrna参与重要的生物过程。MR和BWMR分析证实了“中性粒细胞胞外陷阱形成”通路对NSCLC的抑制作用。免疫学分析确定了与免疫功能相关的高危途径,潜在地增强了高危患者的免疫治疗前景。TMB高的患者总体生存期较差,而高危患者化疗药物敏感性增高。最后,mRNA干细胞指数(mRNAsi)与LUAD患者预后相关。结论:本研究强调了DrugGenoLnc作为预后特征的实用性,为LUAD建立了稳健的预后模型,并为早期检测标志物和治疗靶点识别提供了潜力。此外,它提供了抗肿瘤免疫微环境的见解,指导LUAD的临床治疗策略。
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引用次数: 0
Exploring the potential of probiotics in mercury detoxification: a systematic review 探索益生菌在汞解毒中的潜力:系统综述
Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI: 10.1016/j.meomic.2026.100054
Moulik Bhattacharyya , Serina Easmin , Dipjyoti Sharma , Pollobi Porasar , Tanusree Karmakar , Koushik Nandan Dutta , Ranabir Sahu , Gouranga Nandi , Paramita Paul , Tarun Kumar Dua
Mercury is a very toxic heavy metal that inflicts neurological, reproductive, and metabolic impairment, yet current chelation therapies are constrained in both safety and efficacy. This study assesses the effectiveness of probiotics as a biotherapeutic strategy for mercury detoxification. Probiotics protect by physically sequestering mercury through cell wall components, enhancing antioxidant defenses via the Nrf2/Keap1-ARE signaling pathway, modulating inflammatory responses by downregulating the NF-κB and MAPK pathways, and maintaining intestinal barrier integrity. Translational findings suggest that probiotic therapies may function as economical and culturally acceptable dietary options for mitigating mercury exposure, especially in populations vulnerable due to contaminated food or environmental factors. Research from in vitro models, animal studies, and initial human trials suggests that strains such as Lactobacillus, Bifidobacterium, and Bacillus can bind to and sequester mercury in the gastrointestinal tract, enhance its fecal excretion, convert it into less toxic forms, and restore antioxidant, immune, and intestinal functions. Despite initial encouraging outcomes, extensive clinical studies and the selection of specific strains are necessary to substantiate probiotics as a viable therapeutic strategy for mercury detoxification. This study suggests that probiotics are a safe, sustainable, and promising approach to mitigating mercury toxicity; however, additional clinical validation and strain-specific modifications are necessary.
汞是一种非常有毒的重金属,会造成神经、生殖和代谢障碍,但目前的螯合疗法在安全性和有效性方面都受到限制。本研究评估了益生菌作为汞解毒生物治疗策略的有效性。益生菌通过细胞壁组分对汞进行物理隔离,通过Nrf2/Keap1-ARE信号通路增强抗氧化防御,通过下调NF-κB和MAPK通路调节炎症反应,维持肠道屏障完整性。转化研究结果表明,益生菌疗法可以作为经济和文化上可接受的饮食选择,减轻汞暴露,特别是在易受食物污染或环境因素影响的人群中。来自体外模型、动物研究和初步人体试验的研究表明,乳酸菌、双歧杆菌和芽孢杆菌等菌株可以与胃肠道中的汞结合并隔离汞,增强其粪便排泄,将其转化为毒性较低的形式,并恢复抗氧化、免疫和肠道功能。尽管最初的结果令人鼓舞,但广泛的临床研究和特定菌株的选择是必要的,以证实益生菌作为汞解毒的可行治疗策略。这项研究表明,益生菌是一种安全、可持续和有前途的减轻汞毒性的方法;然而,额外的临床验证和菌株特异性修改是必要的。
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引用次数: 0
Design of a novel multi-epitope-based vaccine against Bundibugyo Ebolavirus using computational approach 利用计算方法设计一种新的基于多表位的本迪布焦埃博拉病毒疫苗
Pub Date : 2026-03-01 Epub Date: 2025-11-24 DOI: 10.1016/j.meomic.2025.100050
Salman Khan , Ishaq Khan , Arshad Iqbal , Syed Shujait Ali , Nisar Ahmad , Sami Ullah , Liaqat Ali , Sajjad Ahmad

Background

Ebola virus (EBOV), a member of the Filoviridae family, is a highly lethal disease that has caused multiple outbreaks primarily in Central Africa. According to the World Health Organization (WHO) report, the Ebola Virus Disease death rate in 2019 was around 67 %. Specifically, Bundibugyo Ebolavirus (BEBOV) has a relatively lower pathogenic mortality rate, estimated at 37 %. Previous epidemics have seen varying death rates ranging from 25 to 95 % due to the lack of effective medicines and immunizations.

Objectives

This study aimed to design a multi-epitope vaccine against BEBOV using immunoinformatics to induce robust immune responses.

Methods and results

T-cell (CTL and HTL) and linear B-cell epitopes from spike glycoprotein and nucleoprotein were identified and screened for antigenicity (VaxiJen score: 0.6488), allergenicity, and immunogenicity. Selected epitopes were combined into a vaccine construct with beta-defensin as an adjuvant. The vaccine exhibited favorable physicochemical properties and solubility (0.863482). Molecular docking and dynamics simulations revealed strong binding to TLR-3 (docking score: −354.13 kcal/mol). Codon optimization and in silico cloning suggested efficient expression in Escherichia coli.

Conclusion and future recommendation

The designed multi-epitope vaccine demonstrates promising immunogenic potential against BEBOV. Experimental validation is required to confirm efficacy and safety, and further studies should focus on optimization and clinical evaluation for potential outbreak prevention.
背景:埃博拉病毒(EBOV)是丝状病毒科的一员,是一种高度致命的疾病,主要在中非引起多次疫情。根据世界卫生组织(WHO)的报告,2019年埃博拉病毒病的死亡率约为67%。具体而言,本迪布焦埃博拉病毒(BEBOV)的致病性死亡率相对较低,估计为37%。由于缺乏有效的药物和免疫接种,以前的流行病死亡率从25%到95%不等。目的利用免疫信息学技术设计BEBOV多表位疫苗,诱导免疫应答。方法与结果对刺突糖蛋白和核蛋白的st细胞(CTL和HTL)和线性b细胞表位进行鉴定,并进行抗原性(VaxiJen评分:0.6488)、过敏原性和免疫原性筛选。选择的表位与β -防御素作为佐剂组合成疫苗结构。该疫苗具有良好的理化性质和溶解度(0.863482)。分子对接和动力学模拟表明,与TLR-3有很强的结合(对接分数:−354.13 kcal/mol)。密码子优化和基因克隆在大肠杆菌中高效表达。结论及未来建议设计的多表位疫苗对BEBOV具有良好的免疫原性。需要实验验证以确认有效性和安全性,进一步的研究应侧重于优化和临床评估,以潜在的疫情预防。
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引用次数: 0
Effects of secretome from areca nut-exposed fibroblast cells on malignant transformation of oral epithelial cells 槟榔暴露成纤维细胞分泌组对口腔上皮细胞恶性转化的影响
Pub Date : 2026-03-01 Epub Date: 2026-02-10 DOI: 10.1016/j.meomic.2026.100055
Tarun Prakash Verma , Sonali Adhikari , Siddharth Singh , Ajay Kumar Meena , Hem Chandra Jha
The intercellular signaling between fibroblast cells and epithelial keratinocytes in oral cavity plays an important role in the malignant transformation of oral submucous fibrosis (OSMF) to oral squamous cell carcinoma (OSCC). Hence, the current study was designed to evaluate the effect of the secretome from the areca nut-exposed fibroblast cells on the oral keratinocytes. We collected the conditioned media (CM) from the fibroblast cells exposed with the areca nut extract (10 µg/ml) for 48 h and transferred it to the keratinocyte cells, followed by incubation for 48 h. We then assessed the cell proliferation, mRNA expression for OSCC-related genes, and metabolomics of the CM and cell lysate by liquid chromatography-mass spectrometry (LCMS). We found a higher proliferation in the cells incubated with exposed CM compared to unexposed CM. The mRNA expression profiles show significant upregulation of five genes (pcsk9, mmp12, inhba, mmp11 and hoxd11). The metabolomics shows alteration of tryptophan metabolism, pyrimidine metabolism, aspartate & asparagine metabolism in CM, and glycolysis and gluconeogenesis in the cell lysate. In conclusion, we identified the genes and pathways that are affected by the secretome from areca nut-exposed fibroblast cells and may have a role in the malignant transformation of oral submucous fibrosis.
口腔成纤维细胞和上皮角质形成细胞之间的细胞间信号在口腔黏膜下纤维化(OSMF)向口腔鳞状细胞癌(OSCC)的恶性转化过程中起重要作用。因此,本研究旨在评估槟榔暴露的成纤维细胞分泌组对口腔角化细胞的影响。我们从槟榔提取物(10µg/ml)暴露48小时的成纤维细胞中收集条件培养基(CM),并将其转移到角质形成细胞中,随后孵育48小时。然后我们通过液相色谱-质谱(LCMS)评估细胞增殖,oscc相关基因的mRNA表达以及CM和细胞裂解物的代谢组学。我们发现,与未暴露的CM相比,暴露CM孵育的细胞增殖率更高。mRNA表达谱显示5个基因(pcsk9、mmp12、inhba、mmp11和hoxd11)显著上调。代谢组学显示CM中色氨酸代谢、嘧啶代谢、天冬氨酸和天冬氨酸代谢以及细胞裂解液中糖酵解和糖异生的改变。总之,我们确定了受槟榔暴露的成纤维细胞分泌组影响的基因和途径,并可能在口腔粘膜下纤维化的恶性转化中发挥作用。
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引用次数: 0
Phytochemical analysis, evaluation of antioxidant activity, and investigation of antibacterial activity in euphorbia candelabrum root extracts 大戟根提取物的植物化学分析、抗氧化活性评价和抗菌活性研究
Pub Date : 2026-03-01 Epub Date: 2025-11-29 DOI: 10.1016/j.meomic.2025.100051
Kifle Jilo Jego , Legesse Adane , Fillipo Tamiru
Euphorbia candelabrum is a medicinal plant traditionally used for treating coughs, tuberculosis, malaria, wound healing, and various skin conditions. This study aimed to analyze the secondary metabolites present in its root extract and evaluate its antioxidant and antibacterial properties. Samples were collected from Sika Kebele in the Gedeo Zone of Southern Ethiopia, air-dried, and then extracted using hexane, dichloromethane, a methanol:dichloromethane mixture (1:1 v/v), and methanol. Phytochemical analysis revealed the presence of alkaloids, flavonoids, phenolics, glycosides, terpenoids, tannins, and saponins in the dichloromethane, methanol:dichloromethane 1:1 mixture, and methanol extracts. In contrast, the hexane extract contained only alkaloids, terpenoids, and steroids. Notably, the methanol:dichloromethane extract yielded flavonoids (10.47 mg QE/g), phenolics (13.4 mg GAE/g), alkaloids (1.426 mg AE/g), and steroids (2.91 mg DME/g). The methanol extract demonstrated higher levels of flavonoids (11 mg QE/g) and phenolics (19 mg GAE/g). Antibacterial activity was assessed against E. coli, P. aeruginosa, S. aureus, and S. pyogenes using the disc diffusion method. The isolated compounds exhibited greater antibacterial activity than crude extracts, with compound KJ-3 showing greater activity against all tested strains, slightly less than tetracycline. These findings suggest that the root of Euphorbia candelabrum may serve as a promising source for the development of new antibacterial agents.
大戟是一种药用植物,传统上用于治疗咳嗽、肺结核、疟疾、伤口愈合和各种皮肤状况。本研究旨在分析其根提取物的次生代谢产物,并评价其抗氧化和抗菌性能。样品从埃塞俄比亚南部Gedeo区的Sika Kebele采集,风干,然后用己烷、二氯甲烷、甲醇:二氯甲烷混合物(1:1 v/v)和甲醇提取。植物化学分析表明,在二氯甲烷、甲醇:二氯甲烷1:1混合物和甲醇提取物中存在生物碱、类黄酮、酚类、苷类、萜类、单宁和皂苷。相比之下,己烷提取物只含有生物碱、萜类和类固醇。值得注意的是,甲醇:二氯甲烷提取物产生黄酮类(10.47 mg QE/g),酚类(13.4 mg GAE/g),生物碱(1.426 mg AE/g)和类固醇(2.91 mg DME/g)。甲醇提取物中黄酮类化合物(11 mg QE/g)和酚类物质(19 mg GAE/g)含量较高。采用圆盘扩散法测定其对大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌和化脓性葡萄球菌的抑菌活性。化合物KJ-3对所有菌株的抑菌活性均高于粗提物,略低于四环素。这些发现表明,大戟根可能是开发新型抗菌药物的一个有希望的来源。
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引用次数: 0
Mezoneuron benthamianum attenuates indomethacin-induced toxicity: Design, synthesis, elemental analysis, in vivo and in silico studies 苯并咪唑胺减少吲哚美辛引起的毒性:设计,合成,元素分析,体内和硅研究
Pub Date : 2025-12-01 Epub Date: 2025-10-24 DOI: 10.1016/j.meomic.2025.100048
Oluwasayo P. Abodunrin , Olayinka F. Onifade , P.M. Osamudiamen , Zacchaeus S. Ololade , Esther O. Abam , Somto O. Otega , Faith O. James , Benjamen O. Okunlola

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain relief and anti-inflammatory effects but can cause significant liver damage and oxidative stress. Mezoneuron benthamianum, a plant with medicinal properties, has been traditionally used for various treatments.

Methods

This study evaluates the hepatoprotective and antioxidant effects of Mezoneuron benthamianum leaves extract against NSAID-induced toxicity in albino rats. Rats were divided into five groups: control, indomethacin-treated, Mezoneuron benthamianum extract-treated, indomethacin and Mezoneuron benthamianum co-treated, and indomethacin and methyl gallate co-treated. The extract’s biochemical composition was analyzed using GC–MS, and liver function biomarkers (ALT, AST, ALP) and biochemical markers (MDA, SOD, CAT, GSH) were measured.

Results and discussion

Results showed that the indomethacin-treated group had significantly increased ALT, AST, and ALP levels, elevated MDA levels, and reduced SOD, CAT, and GSH activities, indicating liver damage and oxidative stress. Treatment with Mezoneuron benthamianum extract significantly reduced these biomarkers and restored antioxidant enzyme activities. Histopathological analysis confirmed reduced liver damage in the extract-treated group, with similar protective effects observed in the indomethacin and methyl gallate co-treated group. The concentration of Cd marginally exceeded WHO’s limit (0.3412 mg/kg vs. 0.3 mg/kg) whereas concentrations of Fe, Mn, and Cu were well below the thresholds. The hepatoprotective and antioxidant effects of Mezoneuron benthamianum extract might be partially mediated through interactions with essential trace elements, such as Fe, Cu, and Mn.

Conclusion

The study reveals that Mezoneuron benthamianum extract attenuated liver damage by restoring antioxidant enzymes (SOD, CAT, GSH) and reducing oxidative stress markers (MDA). Molecular docking suggested PPAR-α activation as a potential mechanism, though further validation is needed. The study highlights its hepatoprotective potential but warrants dose-response studies for clinical translation.
非甾体抗炎药(NSAIDs)广泛用于缓解疼痛和抗炎作用,但可能导致严重的肝损伤和氧化应激。benthamium是一种具有药用价值的植物,传统上用于各种治疗。方法研究本品对非甾体抗炎药(nsaid)致白化大鼠的肝保护和抗氧化作用。将大鼠分为5组:对照组、吲哚美辛组、苯并咪唑脲提取物组、吲哚美辛与苯并咪唑脲共处理组、吲哚美辛与没食子酸甲酯共处理组。采用GC-MS分析提取物的生化成分,测定肝功能生物标志物(ALT、AST、ALP)和生化标志物(MDA、SOD、CAT、GSH)。结果与讨论结果显示,吲哚美辛治疗组大鼠ALT、AST、ALP水平显著升高,MDA水平升高,SOD、CAT、GSH活性降低,提示肝损伤和氧化应激。用苯达胺提取物处理可显著降低这些生物标志物并恢复抗氧化酶活性。组织病理学分析证实,提取物处理组肝损伤减轻,吲哚美辛和没食子酸甲酯共处理组也有类似的保护作用。镉的浓度略高于世卫组织的限值(0.3412 mg/kg vs. 0.3 mg/kg),而铁、锰和铜的浓度远低于阈值。benthamium Mezoneuron benthamium提取物的肝保护和抗氧化作用可能部分通过与必需微量元素(如Fe、Cu和Mn)的相互作用介导。结论本品提取物通过恢复抗氧化酶(SOD、CAT、GSH)和降低氧化应激标志物(MDA)来减轻肝损伤。分子对接提示PPAR-α激活是潜在的机制,但需要进一步验证。该研究强调了其肝保护潜力,但需要进行临床转化的剂量反应研究。
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引用次数: 0
Identification of a prognostic signature for bladder cancer associated with the epithelial-mesenchymal transition hallmark pathway using the TCGA Database 使用TCGA数据库识别与上皮-间质转化标志通路相关的膀胱癌预后标志
Pub Date : 2025-12-01 Epub Date: 2025-11-01 DOI: 10.1016/j.meomic.2025.100049
Shabiha Afroj Heeamoni, Safayat Mahmud Khan, Md. Omar Faruk, Md. Ismail Hosen
Bladder cancer is a common urological malignancy with poor prognosis, underscoring the need for robust prognostic biomarkers. This study investigated gene expression profiles of 194 epithelial-mesenchymal transition (EMT) hallmark genes in 411 muscle-invasive bladder cancer patients from The Cancer Genome Atlas (TCGA). Non-negative matrix factorization identified two subtypes (C1 and C2) with distinct prognostic, clinical, and immunological characteristics. C2 was enriched in EMT-related pathways, including extracellular matrix and structure organization. Differential expression analysis revealed 1,514 prognosis-associated genes. A four-gene prognostic signature—SIGLEC6, NEFL, NTNG1, and FOXC2—was constructed using univariate, LASSO, and multivariate Cox regression models. Patients were stratified into high- and low-risk groups, with the signature demonstrating predictive value in survival analysis and ROC curves. External validation was performed using GEO data. This EMT-based four-gene signature offers a promising prognostic tool for bladder cancer patient stratification and potential therapeutic targeting.
膀胱癌是一种常见的预后不良的泌尿系统恶性肿瘤,因此需要强有力的预后生物标志物。本研究研究了来自癌症基因组图谱(TCGA)的411例肌肉侵袭性膀胱癌患者中194个上皮-间质转化(EMT)标志基因的基因表达谱。非阴性基质因子分析确定了两种亚型(C1和C2),它们具有不同的预后、临床和免疫学特征。C2富集于emt相关通路,包括细胞外基质和结构组织。差异表达分析显示1514个预后相关基因。使用单变量、LASSO和多变量Cox回归模型构建四基因预后特征- siglec6、NEFL、NTNG1和foxc2。将患者分为高危组和低危组,其特征在生存分析和ROC曲线中具有预测价值。使用GEO数据进行外部验证。这种基于emt的四基因标记为膀胱癌患者分层和潜在的治疗靶向提供了一种有希望的预后工具。
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引用次数: 0
Designing a highly antigenic multi epitope subunit vaccine against Bovine alpha herpes virus 2 targeting glycoprotein B and H: A reverse vaccinology approach 设计一种靶向糖蛋白B和H的高抗原多表位亚单位抗牛α疱疹病毒2疫苗:一种反向疫苗学方法
Pub Date : 2025-08-01 Epub Date: 2025-07-12 DOI: 10.1016/j.meomic.2025.100047
Ali Khan, Sara Khan, Muhammad Rahiyab, Salman Khan, Zabih Ullah, Syed Shujait Ali
Bovine alphaherpesvirus 2 (BoHV-2), a major pathogen in cattle, belongs to the Herpesviridae family. In this work, we designed a vaccine against BoHV-2 using its envelope glycoprotein B (gB) and glycoprotein H. In this work, computational methods were utilized for predicting the B and T lymphocyte epitopes with striking results in their antigenicity and low allergenicity. Thereafter, the vaccine design stability tests showed that it was physicochemically stable. Molecular docking and molecular dynamics simulation analyses validated its further efficacy. The docking results demonstrated 11 hydrogen bonds coupled with one salt bridge between the vaccine and TLR3 while PRODIGY analysis suggested a binding free energy (ΔG) of −10.7 kcal/mol alongside a dissociation constant (kDa) of 1.5e-08. In silico cloning demonstrations showed effective expression levels together with immune simulation predictions, suggesting robust immunological responses. However, this study has certain limitations, such as the experimental validation. Future in vivo and in vitro studies are required to confirm the immunogenicity and safety of the in-silico designed vaccine construct.
牛甲疱疹病毒2型(BoHV-2)属于疱疹病毒科,是牛的主要病原体。本研究利用BoHV-2的包膜糖蛋白B (gB)和糖蛋白h设计了一种针对BoHV-2的疫苗。本研究利用计算方法预测了B和T淋巴细胞表位,结果表明它们具有显著的抗原性和低致敏性。此后,疫苗设计稳定性试验表明,它是物理化学稳定的。分子对接和分子动力学模拟分析进一步验证了其有效性。对接结果表明,疫苗与TLR3之间存在11个氢键和1个盐桥,PRODIGY分析表明结合自由能(ΔG)为−10.7 kcal/mol,解离常数(kDa)为1.5e-08。在硅克隆演示显示有效的表达水平和免疫模拟预测,表明稳健的免疫反应。然而,本研究存在一定的局限性,如实验验证。需要进一步的体内和体外研究来确认芯片设计的疫苗结构的免疫原性和安全性。
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引用次数: 0
Multi-omics integration reveals chromatin-associated lncRNA prognostic model in lung adenocarcinoma: Bridging GWAS, transcriptome and clinical outcomes 多组学整合揭示染色质相关lncRNA在肺腺癌中的预后模型:连接GWAS、转录组和临床结果
Pub Date : 2025-08-01 Epub Date: 2025-06-26 DOI: 10.1016/j.meomic.2025.100045
Xiao Zhu , Zhuolong Xiong

Background

Lung adenocarcinoma (LUAD) is characterized by low overall survival rates. This research aims to explore the association between long non-coding RNAs (lncRNAs) and chromatin histone methylation/demethylation modifiers in LUAD.

Methods

Datasets from The Cancer Genome Atlas (TCGA), Molecular Signatures Database (MSigDB), and IEU Open genome-wide association studies (GWAS) database were analyzed. A prognostic risk model for LUAD was developed based on 32 lncRNAs linked to histone modification. The relationship between lncRNAs and the high-risk group of lung cancer was evaluated, and GO/KEGG analysis was conducted to investigate the connection between chromatin histone modification-related lncRNAs and biological processes/pathways. Mendelian Randomization methods, including Inverse Variance Weighted (IVW) and Bayesian Weighted Mendelian Randomization (BWMR), were employed to validate the GO/KEGG results. MR-Egger intercept test, Cochran’s Q test, and leave-one-out Analysis were utilized to assess the sensitivity of Mendelian Randomization analysis. Tumor mutation burden (TMB) analysis was performed to evaluate the prognostic impact of high-risk patients with high TMB.

Results

Identified lncRNAs, including AC025741.1 and NHS-AS1, demonstrated strong associations with the high-risk group. GO/KEGG analysis revealed significant correlations between chromatin histone modification-related lncRNAs and microtubule-based movement and cytochrome enzyme P450. Response to the renin-angiotensin agents is a protective factor for lung cancer, while response to glucocorticoids is a risk factor for lung cancer. Immunomarkers MDSC, CAF, and Exclusion showed positive correlations with the risk score, and the combined effects of CAF and MDSC were found to play a pivotal role in LUAD development and progression.

Conclusion

Our study not only establishes a promising LUAD prognostic risk model with potential implications for immunotherapy but also identifies lncRNAs as immune markers for LUAD immunotherapy. Additionally, we validate the causal relationship between chromatin histone methylation-related pathways and lung cancer, bolstering our understanding from a genetic perspective and opening avenues for targeted interventions in LUAD treatment.
背景:肺腺癌(LUAD)的特点是总生存率低。本研究旨在探讨长链非编码rna (lncRNAs)与LUAD中染色质组蛋白甲基化/去甲基化修饰因子之间的关系。方法对来自癌症基因组图谱(TCGA)、分子特征数据库(MSigDB)和IEU开放全基因组关联研究(GWAS)数据库的数据进行分析。基于32个与组蛋白修饰相关的lncrna,建立了LUAD的预后风险模型。评估lncrna与肺癌高危人群的关系,并通过GO/KEGG分析探讨染色质组蛋白修饰相关lncrna与生物学过程/途径之间的联系。采用孟德尔随机化方法,包括逆方差加权(IVW)和贝叶斯加权孟德尔随机化(BWMR)来验证GO/KEGG结果。采用MR-Egger截距检验、Cochran’s Q检验和留一分析评价孟德尔随机化分析的敏感性。采用肿瘤突变负荷(Tumor mutation burden, TMB)分析,评价高TMB高危患者的预后影响。结果鉴定的lncrna,包括AC025741.1和NHS-AS1,与高危人群有很强的相关性。GO/KEGG分析显示,染色质组蛋白修饰相关lncrna与微管运动和细胞色素酶P450之间存在显著相关性。肾素-血管紧张素药物的反应是肺癌的保护因素,而糖皮质激素的反应是肺癌的危险因素。免疫标记MDSC、CAF和Exclusion与风险评分呈正相关,CAF和MDSC的联合作用在LUAD的发生和进展中起关键作用。结论本研究不仅建立了一个有前景的LUAD预后风险模型,对LUAD免疫治疗具有潜在的指导意义,而且确定了lncrna作为LUAD免疫治疗的免疫标记物。此外,我们验证了染色质组蛋白甲基化相关途径与肺癌之间的因果关系,从遗传学角度加强了我们的理解,并为LUAD治疗的靶向干预开辟了道路。
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引用次数: 0
Analysis of zebrafish homologs within the human genome provides valuable insights into exploring pan-cancer alternative splicing events as prognostic markers and therapeutic targets 分析人类基因组中的斑马鱼同源物为探索泛癌症选择性剪接事件作为预后标志物和治疗靶点提供了有价值的见解
Pub Date : 2025-08-01 Epub Date: 2025-07-08 DOI: 10.1016/j.meomic.2025.100046
Yanjun Liang , Xiao Zhu
Alternative splicing (AS) is pivotal in gene expression regulation and protein diversity generation. Suppression of aberrant AS holds promise in cancer management. Utilizing zebrafish-human homologous genes, we investigated AS events across 33 tumor types from TCGA, employing Cox regression analyses to identify prognostic AS events. A risk-scoring model distinguished high and low-risk groups, revealing differences in survival, tumor microenvironment, and immune cell infiltration. Notably, Complement C1q C Chain (C1QC), DENND5A, HP, IRF5, and LRP1 were associated with poor prognosis and immune infiltration. Mendelian randomization confirmed the protective role of C1QC across cancers, further supported by Bayesian Weighted Mendelian Randomization. Leveraging zebrafish homologs enhances our understanding of AS mechanisms and potential therapeutic targets in cancer biology.
选择性剪接(AS)是基因表达调控和蛋白质多样性产生的关键。抑制异常AS为癌症治疗带来了希望。利用斑马鱼-人类同源基因,我们研究了来自TCGA的33种肿瘤类型的AS事件,采用Cox回归分析来确定预后AS事件。一个风险评分模型区分了高风险组和低风险组,揭示了生存率、肿瘤微环境和免疫细胞浸润的差异。值得注意的是,补体C1q C链(C1QC)、DENND5A、HP、IRF5和LRP1与预后不良和免疫浸润相关。孟德尔随机化证实了C1QC对癌症的保护作用,贝叶斯加权孟德尔随机化进一步支持了这一点。利用斑马鱼的同源物增强了我们对AS机制和癌症生物学中潜在治疗靶点的理解。
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引用次数: 0
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Medicine in Omics
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