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Transcriptomic Landscape of Colorectal Mucinous Adenocarcinoma has Similarity with Intestinal Goblet Cell Differentiation 结直肠黏液腺癌的转录组格局与肠道上皮细胞分化相似
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-03 DOI: 10.2174/0113892029312303240821080358
Jianbo Liu, Siyuan Qiu, Xiaorui Fu, Bin Zhou, Ruijuan Zu, Zhaoying Lv, Yuan Li, Lie Yang, Zongguang Zhou
Introduction: Colorectal mucinous adenocarcinoma (MC) differs from adenocarcinoma (AD) in clinical features and molecular characteristics. The current treatment of colorectal MC is not precise enough, and the molecular characteristics remain unclear. The study aims to explore the difference between colorectal MC and AD on the transcriptome level for the possibility of treating colorectal MC precisely. Methods: The data of colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database was assessed, and then differential analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify the differential hub RNAs between colorectal MC and AD. Differential hub lncRNAs and hub RNA of significant modules were validated by quantitative real-time PCR (qRT-PCR) among different colon cancer cell lines. Results: In total, 1680 differential expressed RNAs (DERs) were found by comparing colorectal MC (52, 13.3%) with AD (340, 86.7%). Through the WGCNA, a mucin-associated RNA module was identified, while some others might be associated with unique immune progress. Finally, 6 differential hub RNAs in the mucin-associated RNA module (CTD-2589M5.4, RP11-234B24.2, RP11-25K19.1 and COLCA1) were validated by qRT-PCR and showed higher expression levels in mucin-producing colorectal cell lines (Ls174T and HT-29). Conclusion: This study suggests that clinical treatments for colorectal MC should be differentiated from AD. Further exploration of enterocyte (goblet cell) differentiation with tumor genesis and the distinct immune progression of MC may help to identify key therapeutic targets for colorectal MC. Further research on the application of immunotherapy to colorectal MC is needed.
导言:结直肠粘液腺癌(MC)与腺癌(AD)在临床特征和分子特征上有所不同。目前对结直肠黏液腺癌的治疗不够精确,其分子特征仍不明确。本研究旨在探讨结直肠MC与AD在转录组水平上的差异,为精确治疗结直肠MC提供可能。研究方法评估癌症基因组图谱(TCGA)数据库中结直肠癌(CRC)患者的数据,然后进行差异分析和加权基因共表达网络分析(WGCNA),以确定结直肠MC和AD之间的差异中枢RNA。在不同的结肠癌细胞系中,通过实时定量 PCR(qRT-PCR)验证了差异中枢 lncRNA 和重要模块的中枢 RNA。结果显示通过比较结直肠癌 MC(52 个,占 13.3%)和结直肠癌 AD(340 个,占 86.7%),总共发现了 1680 个差异表达 RNA(DER)。通过 WGCNA,发现了一个与粘蛋白相关的 RNA 模块,而其他一些 RNA 可能与独特的免疫进展有关。最后,通过 qRT-PCR 验证了粘蛋白相关 RNA 模块中的 6 个差异中枢 RNA(CTD-2589M5.4、RP11-234B24.2、RP11-25K19.1 和 COLCA1),它们在产生粘蛋白的结直肠细胞系(Ls174T 和 HT-29)中的表达水平较高。结论本研究表明,结直肠 MC 的临床治疗应与 AD 区分开来。进一步探讨肠细胞(鹅口疮细胞)分化与肿瘤发生以及 MC 独特的免疫进展可能有助于确定结直肠 MC 的关键治疗靶点。还需要进一步研究免疫疗法在结直肠癌 MC 中的应用。
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引用次数: 0
An Insight into Immunological Therapeutic Approach against Cancer: Potential Anti-Cancer Vaccines 洞察抗癌免疫疗法:潜在的抗癌疫苗
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-02 DOI: 10.2174/0113892029319505240821063238
Arjun Singh Kohli, Somali Sanyal, Radhey Shyam Kaushal, Manish Dwivedi
The development of a cancer vaccine comes with its complications and designing and developing a vaccine against foreign invaders such as bacterial and viral particles is not as complex and multi-faceted as the preparation of immunotherapy for host-infected cells which resemble our own body cells. The entire research and development framework of designing a vaccine for cancerous cells lies entirely on the remarkable aspect of notifying specific interactions and acclimatising the immune system. This review aims to compile the several fronts research-based methodology applies to in terms of developing a therapeutic, preventive or personalised vaccine for cancer . The approach lays focus on the identification and selection of targets for vaccine development which have come to light as immune biomarkers. Furthemore, significant aspects of personalised and precision vaccines and the fine line that runs between these approaches have also been discussed.
癌症疫苗的开发有其复杂性,针对细菌和病毒颗粒等外来入侵者的疫苗设计和开发不如针对类似于自身体细胞的宿主感染细胞的免疫疗法的准备工作复杂和多面。为癌细胞设计疫苗的整个研发框架完全依赖于通知特定的相互作用和适应免疫系统这一重要方面。本综述旨在梳理以研究为基础的方法论在开发癌症治疗、预防或个性化疫苗方面的应用。该方法的重点是识别和选择作为免疫生物标志物的疫苗开发目标。此外,还讨论了个性化和精准疫苗的重要方面以及这些方法之间的细微差别。
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引用次数: 0
Whole Genome Sequences of Cryptotympana Atrata Fabricius, 1775 (Hemiptera: Cicadidae) in the Korean Peninsula: Insights into Population Structure with Novel Pathogenic Or Symbiotic Candidates 朝鲜半岛隐翅虫(Cryptotympana Atrata Fabricius, 1775)(半翅目:蝉科)的全基因组序列:洞察种群结构,发现新的致病或共生候选种
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.2174/0113892029314148240820082402
Jeong Sun Park, Jina Kim, Yeha Kim, Ki Hwan Kim, Woori Kwak, Iksoo Kim
Background: The blackish cicada (Cryptotympana atrata) exhibits unique characteristics and is one of the model cicadas found in the Korean Peninsula. It is a species of southern origin, prefers high temperatures, and is listed as a climate-sensitive indicator species in South Korea. Therefore, this species can be utilized to study the impact of climate change on the genetic diversity and structure of populations. However, research on the genome of C. atrata is limited. Methods: We sequenced the genome of an individual collected from South Korea and constructed a draft genome. Additionally, we collected ten specimens from each of the five regions in South Korea and identified single nucleotide variants (SNVs) for population genetic analysis. The sequencing library was constructed using the MGIEasy DNA Library Prep Kit and sequenced using the MGISEQ-2000 platform with 150-bp paired-end reads. Results: The draft genome of C. atrata was approximately 5.0 Gb or 5.2 Gb, making it one of the largest genomes among insects. Population genetic analysis, which was conducted on four populations in South Korea, including both previously distributed and newly expanded regions, showed that Jeju Island, a remote southern island with the highest average temperature, formed an independent genetic group. However, there were no notable genetic differences among the inland populations selected based on varying average temperatures, indicating that the current population genetic composition on the Korean Peninsula is more reflective of biogeographic history rather than climate- induced genetic structures. Additionally, we unexpectedly observed that most individuals of C. atrata collected in a specific locality were infected with microbes not commonly found in insects, necessitating further research on the pathogens within C. atrata. Conclusion: This study introduces the draft genome of C. atrata, a climate-sensitive indicator species in South Korea. Population analysis results indicate that the current genetic structure of C. atrata is driven by biogeographic history rather than just climate. The prevalence of widespread pathogen infections raises concerns about their impact on C. atrata. Considering the scarcity of publicly available genomic resources related to the family Cicadidae, this draft genome and population data of C. atrata are expected to serve as a valuable resource for various studies utilizing cicada genomes.
背景:黑蝉(Cryptotympana atrata)具有独特的特征,是朝鲜半岛发现的模范蝉之一。它原产于南方,喜欢高温,在韩国被列为气候敏感指示物种。因此,该物种可用于研究气候变化对种群遗传多样性和结构的影响。然而,对 C. atrata 基因组的研究还很有限。方法:我们对从韩国采集的一个个体进行了基因组测序,并构建了基因组草案。此外,我们还从韩国的五个地区各采集了十个标本,并鉴定了单核苷酸变体(SNV),用于种群遗传分析。我们使用 MGIEasy DNA 文库制备试剂盒构建了测序文库,并使用 MGISEQ-2000 平台对 150-bp 的成对端读数进行了测序。结果C. atrata的基因组草案约为5.0 Gb或5.2 Gb,是昆虫中最大的基因组之一。对韩国的四个种群(包括以前分布的地区和新扩展的地区)进行的种群遗传分析表明,平均气温最高的南部偏远岛屿济州岛形成了一个独立的遗传群体。然而,根据不同的平均气温选出的内陆种群之间并没有明显的遗传差异,这表明朝鲜半岛目前的种群遗传组成更多反映的是生物地理历史,而不是气候引起的遗传结构。此外,我们还意外地发现,在某一特定地点采集到的大多数姬蛙个体都感染了昆虫体内不常见的微生物,因此有必要对姬蛙体内的病原体进行进一步研究。结论本研究介绍了韩国气候敏感指示物种 C. atrata 的基因组草案。种群分析结果表明,C. atrata 目前的遗传结构是由生物地理历史而不仅仅是气候驱动的。大范围的病原体感染引发了对 C. atrata 影响的担忧。考虑到与蝉科相关的公开基因组资源稀缺,该蝉基因组草案和种群数据有望成为利用蝉基因组进行各种研究的宝贵资源。
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引用次数: 0
ResUbiNet: A Novel Deep Learning Architecture for Ubiquitination Site Prediction ResUbiNet:用于泛素化位点预测的新型深度学习架构
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.2174/0113892029331751240820111158
Zixin Duan, Yafeng Liang, Xin Xiu, Wenjie Ma, Hu Mei
Introduction: Ubiquitination, a unique post-translational modification, plays a cardinal role in diverse cellular functions such as protein degradation, signal transduction, DNA repair, and regulation of cell cycle. Method: Thus, accurate prediction of potential ubiquitination sites is an urgent requirement for exploring the ubiquitination mechanism as well as the disease pathogenesis associated with ubiquitination processes. Results: This study introduces a novel deep learning architecture, ResUbiNet, which utilized a protein language model (ProtTrans), amino acid properties, and BLOSUM62 matrix for sequence embedding and multiple state-of-the-art architectural components, i.e., transformer, multi-kernel convolution, residual connection, and squeeze-and-excitation for feature extractions. Conclusion: The results of cross-validation and external tests showed that the ResUbiNet model achieved better prediction performances in comparison with the available hCKSAAP_UbSite, RUBI, MDCapsUbi, and MusiteDeep models.
简介泛素化是一种独特的翻译后修饰,在蛋白质降解、信号转导、DNA 修复和细胞周期调控等多种细胞功能中发挥着重要作用。方法:因此,准确预测潜在泛素化位点是探索泛素化机制以及与泛素化过程相关的疾病发病机制的迫切需要。研究结果本研究介绍了一种新型深度学习架构--ResUbiNet,该架构利用蛋白质语言模型(ProtTrans)、氨基酸属性和 BLOSUM62 矩阵进行序列嵌入,并利用多种最先进的架构组件(即变压器、多核卷积、残差连接和挤压-激发)进行特征提取。结论交叉验证和外部测试的结果表明,与现有的 hCKSAAP_UbSite、RUBI、MDCapsUbi 和 MusiteDeep 模型相比,ResUbiNet 模型取得了更好的预测性能。
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引用次数: 0
Genomic Face-Off: An In Silico Comparison of the Probiotic Potential of Lactobacillus spp. and Akkermansia muciniphila 基因组对决:乳酸杆菌属和粘液酵母菌益生菌潜力的硅学比较
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-26 DOI: 10.2174/0113892029317403240815044408
Nayeema Bulbul, Jinath Sultana, Ashrafus Safa, Md. Asaduzzaman Shishir, Bakhtiar Ul Islam, Md. Fakruddin, Md. Abu Bakar karim
Introduction: The gut microbiota plays a crucial role in maintaining human health, and probiotics have gained significant attention for their potential benefits. Among the diverse array of gut bacteria, Akkermansia muciniphila, and Lactobacillus spp. have emerged as promising candidates for their putative probiotic properties. Method: In this study, we conducted a comprehensive comparative in silico analysis of the genomes of A. muciniphila and Lactobacillus to decipher their probiotic potential. Utilizing a range of bioinformatics tools, we evaluated various genomic attributes, including functional gene content, metabolic pathways, antimicrobial peptide production, adhesion factors, and stress response elements. These findings revealed distinctive genomic signatures between the two genera. A. muciniphila genomes exhibited a high prevalence of mucin-degrading enzymes, suggesting a specialized adaptation for mucin utilization in the gut environment. Results: Additionally, the presence of specific pathways for short-chain fatty acid production highlighted its potential impact on host health. Lactobacillus genomes, on the other hand, demonstrated a diverse repertoire of functional genes associated with probiotic attributes, including the production of antimicrobial peptides and adhesion factors, indicating potential for host-microbe interactions and immune modulation. Furthermore, this analysis unveiled the genetic basis of stress tolerance in both genera, revealing conserved mechanisms for surviving the dynamic conditions of the gut ecosystem. Conclusion: This study also shed light on the distribution of antibiotic-resistance genes, allowing us to assess safety concerns associated with their potential use as probiotics. Overall, this comparative in silico exploration provides valuable insights into the genomic foundation of A. muciniphila and Lactobacillus probiotic potential. These findings contribute to the understanding of their respective roles within the gut microbiota and offer a foundation for further experimental investigations. As probiotic applications continue to expand, this study advances our knowledge of the genetic underpinnings that govern their functionality and highlights promising avenues for future therapeutic interventions and personalized health strategies.
导言:肠道微生物群在维持人体健康方面发挥着至关重要的作用,益生菌因其潜在的益处而备受关注。在多种多样的肠道细菌中,Akkermansia muciniphila 和乳酸杆菌因其潜在的益生特性而成为有希望的候选菌。研究方法在本研究中,我们对粘液鞘氨醇和乳酸杆菌的基因组进行了全面的比较硅分析,以解读它们的益生潜力。利用一系列生物信息学工具,我们评估了各种基因组属性,包括功能基因含量、代谢途径、抗菌肽生产、粘附因子和应激反应元件。这些发现揭示了两个属之间独特的基因组特征。A. muciniphila基因组中粘蛋白降解酶的含量较高,这表明它们专门适应了肠道环境中粘蛋白的利用。结果:此外,短链脂肪酸生产的特殊途径突出了其对宿主健康的潜在影响。另一方面,乳酸杆菌基因组展示了与益生菌属性相关的多种功能基因,包括生产抗微生物肽和粘附因子,这表明乳酸杆菌具有宿主-微生物相互作用和免疫调节的潜力。此外,这项分析还揭示了这两个菌属耐受压力的遗传基础,揭示了在肠道生态系统动态条件下生存的保守机制。结论这项研究还揭示了抗生素耐药性基因的分布情况,使我们能够评估与它们可能用作益生菌相关的安全问题。总之,这项硅学比较探索为了解粘多糖酵母菌和乳酸杆菌益生菌潜力的基因组基础提供了宝贵的见解。这些发现有助于人们了解它们各自在肠道微生物群中的作用,并为进一步的实验研究奠定了基础。随着益生菌应用范围的不断扩大,这项研究增进了我们对支配益生菌功能的基因基础的了解,并为未来的治疗干预和个性化健康策略指明了前景广阔的途径。
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引用次数: 0
An Assessment of the Degradation Potential and Genomic Insights Towards Hydroxylated Biphenyls by Rhodococcus opacus Strain KT112-7 评估乳清红球菌 KT112-7 株对羟基联苯的降解潜力和基因组见解
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-22 DOI: 10.2174/0113892029319746240812051356
Darya Egorova, Bjorn Olsson, Tatyana Kir'yanova, Elena Plotnikova
Background: Hydroxylated biphenyls are currently recognized as secondary pollutants that are hazardous to animals and humans. Bacterial degradation is the most effective method for the degradation of hydroxylated biphenyls. Several strains capable of degrading polychlorinated biphenyls have been described, which also degrade hydroxylated biphenyls. Objectives: 1) To study the biodegradative properties of the Rhodococcus opacus strain KT112-7 towards mono-hydroxylated biphenyls. 2) To analyze the genome of the Rhodococcus opacus strain KT112-7. 3) To identify the genetic basis for the unique biodegradative potential of the Rhodococcus opacus strain KT112-7. Methods: A genome analysis of the strain KT112-7 was conducted based on whole-genome sequencing using various programs and databases (Velvet, CONTIGuator, RAST, KEGG) for annotation and identification of protein-coding sequences. The strain KT112-7 was cultivated in a K1 mineral medium supplemented with mono-hydroxy biphenyls or mono-hydroxybenzoic acids as the carbon source. For the growth test mono-hydroxybiphenyls or mono-hydroxybenzoic acids were dosed at concentrations of 0.5 g/L and 1.0 g/L correspondently, and the bacterial growth was monitored by the optical density. For the biodegradative activity test, mono-hydroxybiphenyls were dosed at a concentration of 0.1 g/L in vials, inoculated with late exponential phase bacteria previously acclimated on biphenyl. Compound analysis was performed using GC-MS, HPLC, and spectrophotometry. Results: It was found that the genome of strain KT112-7 consists of a chromosome and 2 plasmids. Biphenyl degradation genes (bph genes) were identified on plasmid PRHWK1 and the chromosome, as well as hydroxybenzoic acid degradation genes on the chromosome. The strain KT112-7 was shown to degrade mono-hydroxylated biphenyls to basal metabolic compounds of the cell, with the highest destructive activity observed towards 3- and 4-hydroxylated biphenyls (98%). Conclusion: The Rhodococcus opacus strain KT112-7 is characterized by genetic systems that contribute to its high biodegradative potential towards mono-hydroxylated biphenyls and their metabolites. Thus, the strain KT112-7 is promising for use in hydroxybiphenyl degradation technologies.
背景:羟基联苯是目前公认的对动物和人类有害的二次污染物。细菌降解是降解羟基联苯的最有效方法。已经描述了几种能够降解多氯联苯的菌株,它们也能降解羟基化联苯。目标1) 研究 Rhodococcus opacus 菌株 KT112-7 对单羟基联苯的生物降解特性。2) 分析乳白念珠菌菌株 KT112-7 的基因组。3) 确定乳白葡萄球菌菌株 KT112-7 具有独特生物降解潜力的遗传基础。研究方法利用各种程序和数据库(Velvet、CONTIGuator、RAST、KEGG)对菌株 KT112-7 进行全基因组测序,并对蛋白质编码序列进行注释和鉴定。菌株 KT112-7 在以单羟基联苯或单羟基苯甲酸为碳源的 K1 矿物培养基中培养。在生长试验中,单羟基联苯或单羟基苯甲酸的浓度分别为 0.5 克/升和 1.0 克/升,细菌生长情况通过光密度进行监测。在生物降解活性测试中,将浓度为 0.1 克/升的单羟基联苯装入小瓶中,并接种先前已适应联苯的晚期指数期细菌。采用气相色谱-质谱法、高效液相色谱法和分光光度法进行化合物分析。结果发现菌株 KT112-7 的基因组由一个染色体和两个质粒组成。在质粒 PRHWK1 和染色体上发现了联苯降解基因(bph 基因),在染色体上也发现了羟基苯甲酸降解基因。研究表明,菌株 KT112-7 能将单羟基联苯降解为细胞的基础代谢化合物,对 3 和 4-羟基联苯的破坏活性最高(98%)。结论Rhodococcus opacus 菌株 KT112-7 的遗传系统有助于提高其对单羟基联苯及其代谢物的生物降解潜力。因此,KT112-7 菌株有望用于羟基联苯降解技术。
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引用次数: 0
High-Throughput Sequencing Revealing BCR and TCR Repertoires as Potential Prognostic Biomarkers for Pediatric Patients with B-ALL 高通量测序揭示 BCR 和 TCR 重排是小儿 B-ALL 患者潜在的预后生物标志物
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-22 DOI: 10.2174/0113892029319425240813074610
Fu Li, Xiaomei Yang, Xiuxiu Wang, Jiajia Mi, Xiao Mou, Li Song, Libo Zheng
Background: B-ALL is a hematologic malignancy that recurs in approximately 10-20% of children and has a poor prognosis. New prognostic biomarkers are needed to improve individualized therapy and achieve better clinical outcomes. Methods: In this study, high-throughput sequencing technology was used to detect the BCR and TCR repertoires in children with B-ALL. Results: We observed a gradual increase in the diversity of the BCR and TCR repertoires during the developmental stages (Pro-, Common-, Pre-B-ALL) of precursor B-ALL cells. Conversely, as minimal residual disease (MRD) levels on day 19 of induction therapy increased, the BCR/TCR repertoire diversity decreased. Furthermore, the BCR/TCR repertoire diversity was significantly greater in B-ALL patients at low risk and those harboring the ETV6/RUNX1 fusion than in patients with medium-risk disease and those harboring the ZNF384 fusion. Notably, the abundance of BCR/TCR clones varied significantly among patients with B-ALL and different clinical characteristics. Specifically, patients with Pre-B-ALL, low-risk disease, D19MRD levels <1%, and harboring the ETV6/RUNX1 fusion exhibited a predominance of BCR/TCR small clones. In our study, we noted an imbalanced occurrence of V and J gene utilization among patients with BALL; however, there seemed to be no discernible correlation with the clinical attributes. Conclusion: BCR/TCR repertoires are expected to be potential prognostic biomarkers for patients with B-ALL.
背景:B-ALL是一种血液系统恶性肿瘤,约有10%-20%的儿童会复发,且预后较差。需要新的预后生物标志物来改善个体化治疗并获得更好的临床疗效。研究方法本研究采用高通量测序技术检测 B-ALL 儿童的 BCR 和 TCR 重排。结果我们观察到,在前体 B-ALL 细胞的发育阶段(Pro-、Common、Pre-B-ALL),BCR 和 TCR 重排的多样性逐渐增加。相反,随着诱导治疗第 19 天最小残留病(MRD)水平的升高,BCR/TCR 反应序列的多样性也随之降低。此外,低风险和携带 ETV6/RUNX1 融合基因的 B-ALL 患者的 BCR/TCR 基因库多样性明显高于中度风险和携带 ZNF384 融合基因的患者。值得注意的是,不同临床特征的B-ALL患者的BCR/TCR克隆丰度差异很大。具体来说,Pre-B-ALL、低风险疾病、D19MRD水平为1%和携带ETV6/RUNX1融合基因的患者主要表现为BCR/TCR小克隆。在我们的研究中,我们注意到 BALL 患者的 V 和 J 基因利用率不平衡,但似乎与临床属性没有明显的相关性。结论BCR/TCR 重排有望成为 B-ALL 患者潜在的预后生物标志物。
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引用次数: 0
The Regulatory Landscape of Biobanks In Europe: From Accreditation to Intellectual Property 欧洲生物库的监管格局:从认证到知识产权
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-31 DOI: 10.2174/0113892029313697240729091922
Antonella Corradi, Giuseppina Bonizzi, Elham Sajjadi, Francesca Pavan, Marzia Fumagalli, Luigi Orlando Molendini, Massimo Monturano, Cristina Cassi, Camilla Rosella Musico, Luca Leoni, Chiara Frascarelli, Oriana Pala, Elena Guerini-Rocco, Adriana Albini, Roberto Orecchia, Nicola Fusco
: Biobanks are necessary resources for the storage and management of human biological materials, such as biofluids, tissues, cells, or nucleotides. They play a significant role in the development of new treatments and the advancement of basic and translational research, especially in the field of biomarkers discovery and validation. The regulatory landscape for biobanks, which is necessary to safeguard both privacy and scientific discoveries, exhibits significant heterogeneity across different countries and regions. This article outlines the standards that modern biobanks should fulfill in the European Union (EU), including general, structural, resource, process, and quality requirements. Special attention is given to the importance of transparency and donor consent following the General Data Protection Regulation (GDPR) and the ISO 20387:2018, the international standard specifies general requirements for biobanks. A dedicated section covers the preparation of donor information materials, emphasizing consent for research involvement and personal data processing. The delicate balance between donors' privacy rights and scientific research promotion is also discussed, with a focus on the patenting and economic use of biological material- derived inventions and data. Considering these factors, it would be warranted to refine legal frameworks and foster interdisciplinary collaboration to ethically and responsibly expand biobanking.
:生物库是储存和管理人类生物材料(如生物液体、组织、细胞或核苷酸)的必要资源。它们在开发新的治疗方法、推进基础研究和转化研究方面发挥着重要作用,尤其是在生物标志物的发现和验证领域。生物库是保护隐私和科学发现的必要条件,但不同国家和地区对生物库的监管存在很大差异。本文概述了欧盟(EU)现代生物库应达到的标准,包括一般、结构、资源、流程和质量要求。文章特别关注了《一般数据保护条例》(GDPR)和国际标准 ISO 20387:2018 规定的生物库一般要求中透明度和捐献者同意的重要性。其中专门有一节涉及捐赠者信息材料的准备,强调同意参与研究和个人数据处理。此外,还讨论了捐赠者隐私权与促进科学研究之间的微妙平衡,重点关注生物材料衍生发明和数据的专利申请和经济用途。考虑到这些因素,有必要完善法律框架,促进跨学科合作,以合乎伦理和负责任的方式扩大生物库。
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引用次数: 0
Integrative Bioinformatics Analysis for Targeting Hub Genes in Hepatocellular Carcinoma Treatment 针对肝细胞癌治疗中枢基因的综合生物信息学分析
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-22 DOI: 10.2174/0113892029308243240709073945
Indu Priya Gudivada, Krishna Chaitanya Amajala
Background: The damage in the liver and hepatocytes is where the primary liver cancer begins, and this is referred to as Hepatocellular Carcinoma (HCC). One of the best methods for detecting changes in gene expression of hepatocellular carcinoma is through bioinformatics approaches. Objective: This study aimed to identify potential drug target(s) hubs mediating HCC progression using computational approaches through gene expression and protein-protein interaction datasets. Methodology: Four datasets related to HCC were acquired from the GEO database, and Differentially Expressed Genes (DEGs) were identified. Using Evenn, the common genes were chosen. Using the Fun Rich tool, functional associations among the genes were identified. Further, protein-protein interaction networks were predicted using STRING, and hub genes were identified using Cytoscape. The selected hub genes were subjected to GEPIA and Shiny GO analysis for survival analysis and functional enrichment studies for the identified hub genes. The up-regulating genes were further studied for immunohistopathological studies using HPA to identify gene/protein expression in normal vs HCC conditions. Drug Bank and Drug Gene Interaction Database were employed to find the reported drug status and targets. Finally, STITCH was performed to identify the functional association between the drugs and the identified hub genes. Results: The GEO2R analysis for the considered datasets identified 735 upregulating and 284 downregulating DEGs. Functional gene associations were identified through the Fun Rich tool. Further, PPIN network analysis was performed using STRING. A comparative study was carried out between the experimental evidence and the other seven data evidence in STRING, revealing that most proteins in the network were involved in protein-protein interactions. Further, through Cytoscape plugins, the ranking of the genes was analyzed, and densely connected regions were identified, resulting in the selection of the top 20 hub genes involved in HCC pathogenesis. The identified hub genes were: KIF2C, CDK1, TPX2, CEP55, MELK, TTK, BUB1, NCAPG, ASPM, KIF11, CCNA2, HMMR, BUB1B, TOP2A, CENPF, KIF20A, NUSAP1, DLGAP5, PBK, and CCNB2. Further, GEPIA and Shiny GO analyses provided insights into survival ratios and functional enrichment studied for the hub genes. The HPA database studies further found that upregulating genes were involved in changes in protein expression in Normal vs HCC tissues. These findings indicated that hub genes were certainly involved in the progression of HCC. STITCH database studies uncovered that existing drug molecules, including sorafenib, regorafenib, cabozantinib, and lenvatinib, could be used as leads to identify novel drugs, and identified hub genes could also be considered as potential and promising drug targets as they are involved in the gene-chemical interaction networks. Conclusion: The present study involved various integrated bioinformatics approaches, analyzing gen
背景:肝脏和肝细胞的损伤是原发性肝癌的起始部位,被称为肝细胞癌(HCC)。检测肝细胞癌基因表达变化的最佳方法之一是生物信息学方法。研究目的本研究旨在通过基因表达和蛋白质相互作用数据集,利用计算方法确定介导 HCC 进展的潜在药物靶点。研究方法:从 GEO 数据库中获取与 HCC 相关的四个数据集,并确定差异表达基因(DEG)。利用Evenn选择常见基因。使用 Fun Rich 工具确定了基因之间的功能关联。此外,还使用 STRING 预测了蛋白质-蛋白质相互作用网络,并使用 Cytoscape 确定了中心基因。对选定的中心基因进行 GEPIA 和 Shiny GO 分析,以对已确定的中心基因进行生存分析和功能富集研究。利用 HPA 进一步对上调基因进行免疫组织病理学研究,以确定正常与 HCC 条件下的基因/蛋白质表达情况。利用药物库和药物基因相互作用数据库查找报告的药物状态和靶点。最后,采用 STITCH 方法确定药物与已确定的枢纽基因之间的功能关联。结果对数据集进行的 GEO2R 分析确定了 735 个上调 DEGs 和 284 个下调 DEGs。通过 Fun Rich 工具确定了功能基因关联。此外,还使用 STRING 进行了 PPIN 网络分析。在 STRING 中对实验证据和其他七个数据证据进行了比较研究,发现网络中的大多数蛋白质都参与了蛋白质之间的相互作用。此外,还通过 Cytoscape 插件对基因的排序进行了分析,确定了连接密集的区域,从而选出了涉及 HCC 发病机制的前 20 个枢纽基因。确定的枢纽基因有这些基因包括:KIF2C、CDK1、TPX2、CEP55、MELK、TTK、BUB1、NCAPG、ASPM、KIF11、CCNA2、HMMR、BUB1B、TOP2A、CENPF、KIF20A、NUSAP1、DLGAP5、PBK 和 CCNB2。此外,GEPIA 和 Shiny GO 分析还提供了对枢纽基因的存活率和功能富集研究的见解。HPA 数据库研究进一步发现,上调基因参与了正常组织与 HCC 组织蛋白质表达的变化。这些发现表明,中心基因肯定与 HCC 的进展有关。STITCH 数据库研究发现,索拉非尼、瑞戈非尼、卡博赞替尼和来伐替尼等现有药物分子可作为新药研发的线索。结论本研究采用了多种综合生物信息学方法,分析了基因表达和蛋白质相互作用数据集,最终确定了 20 个与 HCC 进展相关的顶级中心基因。它们是KIF2C、CDK1、TPX2、CEP55、MELK、TTK、BUB1、NCAPG、ASPM、KIF11、CCNA2、HMMR、BUB1B、TOP2A、CENPF、KIF20A、NUSAP1、DLGAP5、PBK和CCNB2。基因-化学相互作用网络研究发现,现有的药物分子,包括索拉非尼、瑞戈非尼、卡博赞替尼和来伐替尼,都可以作为鉴定新药的线索,而鉴定出的枢纽基因可以成为有希望的药物靶点。本研究强调了靶向这些枢纽基因和利用现有分子生成新分子以有效抗击肝癌的意义,并可在药物发现研究方面进一步探索开发 HCC 的治疗方法。
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引用次数: 0
Melocular Evolution on Cold Temperature Adaptation of Chinese Rhesus Macaques 中国猕猴寒冷温度适应的黑眼进化
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-11 DOI: 10.2174/0113892029301969240708094053
Xuan Wang, Ming-Hong Feng, Shao-Bo Wang, Hong Shi
Introduction: Currently, macaques are used as animal models for human disease in biomedical research. There are two macaques species widely used as animal models, i.e., cynomolgus macaques and rhesus macaques. Method: These two primates distribute widely, and their natural habitats are different. Cynomolgus macaques distribute in tropical climates, while rhesus macaques mostly distribute in relatively cold environments, and cynomolgus macaques have a common frostbite problem during winter when they are transferred to cold environments. In order to explore the molecular mechanisms underlying the temperature adaptation in macaques, genetic analysis and natural selection tests were performed. Based on the analysis of heat shock protein genes, DNAJC22, DNAJC28, and HSF5 showed positive selection signals. To these 3 genes, the significantly differential expression had been confirmed between cynomolgus macaques and Chinese rhesus macaques. Molecular evolution analysis showed that mutations of DNAJC22, DNAJC28, and HSF5 in Chinese rhesus macaques could enable them to gain the ability to rapidly regulate body temperature. The heat shock proteins provided an important function for Chinese rhesus macaques, allowing them to adapt to a wide range of temperatures and spread widely. Results: The selection time that was estimated suggested that the cold adaptation of Chinese rhesus macaques coincided with the time that the modern human populations migrated northward from tropic regions to relatively cold regions, and the selection genes were similar. Conclusion: This study elucidated the evolutionary history of cynomolgus macaques and rhesus macaques from molecular adaptation. Furthermore, it provided an evolutionary perspective to reveal the different distribution and adaptation of macaques. Cynomolgus macaques is an ideal biomedical animal model to mimic human natural frostbite.
简介目前,猕猴在生物医学研究中被用作人类疾病的动物模型。被广泛用作动物模型的猕猴有两种,即猕猴和恒河猴。研究方法这两种灵长类动物分布广泛,自然栖息地也不同。猕猴分布在热带气候地区,而猕猴大多分布在相对寒冷的环境中,猕猴在冬季被转移到寒冷环境中时常见冻伤问题。为了探索猕猴温度适应的分子机制,研究人员进行了遗传分析和自然选择试验。根据对热休克蛋白基因的分析,DNAJC22、DNAJC28和HSF5出现了正选择信号。这三个基因在猕猴和中国猕猴之间存在明显的表达差异。分子进化分析表明,中国猕猴DNAJC22、DNAJC28和HSF5的突变可使其获得快速调节体温的能力。热休克蛋白为中国猕猴提供了重要功能,使它们能够适应各种温度并广泛传播。研究结果估计的选择时间表明,中国猕猴对寒冷的适应与现代人类从热带地区向北迁移到相对寒冷地区的时间相吻合,而且选择基因相似。结论本研究从分子适应的角度阐明了猕猴和猕猴的进化历史。此外,该研究还从进化的角度揭示了猕猴的不同分布和适应性。猕猴是模拟人类自然冻伤的理想生物医学动物模型。
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Current Genomics
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