Pathology, research and practice最新文献_第4页

OTUD7B promotes cell migration and invasion, predicting poor prognosis of gastric cancer OTUD7B 促进细胞迁移和侵袭，可预测胃癌的不良预后。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-31 DOI: 10.1016/j.prp.2024.155689

Xiao-Li Liu , Shan-Yu Zhao , Ming-Hui Zhang , Ping-Zhao Zhang , Xiu-Ping Liu

Background

OTUD7B, a member of the ovarian tumor (OTU) protein superfamily, functions as a deubiquitinating enzyme and is associated with various biological processes and disease conditions, including tumors. In this study, we aimed to explore the expression patterns, prognostic significance, and the functional roles and underlying mechanisms of OTUD7B in gastric cancer (GC).

Materials and methods

Using a blend of bioinformatics, clinical case reviews, and molecular experiments, we evaluated the expression of OTUD7B in GC at both mRNA and protein levels. We examined the relationship between OTUD7B expression and clinicopathological characteristics of GC patients. Additionally, in vitro assays were utilized to assess the effects of OTUD7B on the migratory and invasive capabilities of GC cells. RNA sequencing analysis was conducted to identify critical genes and pathways linked to OTUD7B in GC.

Results

OTUD7B was found to be significantly overexpressed in GC, both at mRNA and protein levels. Higher levels of OTUD7B were positively associated with advanced tumor TNM stage, higher histological grade, and presence of lymph/vein invasion. These correlations were indicative of poorer overall survival (OS) and disease-free survival (DFS) in GC patients. In vitro assays revealed that genetic knockout of OTUD7B markedly reduced the migration and invasion of GC cells, while overexpression of OTUD7B led to enhanced cellular migration and invasion. Furthermore, RNA sequencing and bioinformatic analyses indicated that the absence of OTUD7B suppressed signaling pathways related to cancer progression, metastasis, and metabolism. Mechanistically, OTUD7B likely promotes GC metastasis through the WNT signaling pathway, specifically targeting β-catenin.

Conclusions

OTUD7B serves as a novel marker for poor prognosis in GC and actively promotes tumor metastasis. Our results shed light on the signaling pathways regulated by OTUD7B and highlight potential targets for therapeutic intervention.

背景：OTUD7B是卵巢肿瘤（OTU）蛋白超家族的成员，作为一种去泛素化酶发挥作用，与包括肿瘤在内的多种生物过程和疾病相关。本研究旨在探讨 OTUD7B 在胃癌（GC）中的表达模式、预后意义、功能作用及其内在机制：采用生物信息学、临床病例回顾和分子实验相结合的方法，我们评估了 OTUD7B 在 GC 中 mRNA 和蛋白水平的表达。我们研究了 OTUD7B 表达与 GC 患者临床病理特征之间的关系。此外，我们还利用体外实验评估了 OTUD7B 对 GC 细胞迁移和侵袭能力的影响。研究人员还进行了 RNA 测序分析，以确定 GC 中与 OTUD7B 相关的关键基因和通路：结果：研究发现，OTUD7B在GC中的mRNA和蛋白质水平均显著过表达。较高水平的OTUD7B与肿瘤TNM分期晚期、组织学分级较高以及淋巴/静脉侵犯呈正相关。这些相关性表明 GC 患者的总生存期（OS）和无病生存期（DFS）较差。体外实验显示，基因敲除 OTUD7B 会显著降低 GC 细胞的迁移和侵袭，而过表达 OTUD7B 则会增强细胞的迁移和侵袭。此外，RNA 测序和生物信息学分析表明，缺乏 OTUD7B 会抑制与癌症进展、转移和代谢相关的信号通路。从机理上讲，OTUD7B可能通过WNT信号通路促进GC转移，特别是针对β-catenin：结论：OTUD7B是GC预后不良的新标志物，并能积极促进肿瘤转移。我们的研究结果揭示了OTUD7B调控的信号通路，并突出了治疗干预的潜在靶点。

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引用次数: 0

Genetic Polymorphism in miRNA Genes and Their Association with susceptibility of Coronary Heart Disease: anAn Updated Rreview miRNA 基因的遗传多态性及其与冠心病易感性的关系：最新综述。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-30 DOI: 10.1016/j.prp.2024.155675

Khalid Khan , Aakif khan , Zia Ur Rahman , Faisal Khan , Noreen Latief , Numan Fazal

Coronary heart disease (CHD) remains a major public health concern worldwide, with a complex interplay of genetic, environmental and lifestyle factors contributing to its pathogenesis. The potential significance of microRNAs (miRNAs) in the onset and progression of CHD has attracted increasing attention in recent years. Small non-coding RNA molecules called miRNAs control gene expression at the post-transcriptional level. Dysregulation of miRNAs has been linked to a variety of biological processes, including cell division, proliferation, apoptosis, and inflammation. Numerous research studies have looked into the relationship between genetic variants in miRNA genes and CHD susceptibility. This review highlights the recent research work carried out to identify the relationship of miRNA genes polymorphism with the progression and susceptibility of CHD. Such studies could pave the way for the development of personalized strategies for CHD prevention and treatment based on an individual's genetic profile.

冠心病（CHD）仍然是全球关注的主要公共卫生问题，其发病机制是由遗传、环境和生活方式等因素复杂地相互作用造成的。近年来，微小核糖核酸（miRNA）在冠心病发病和发展过程中的潜在意义日益受到关注。被称为 miRNA 的非编码 RNA 小分子在转录后水平控制基因表达。miRNA 的失调与多种生物过程有关，包括细胞分裂、增殖、凋亡和炎症。许多研究探讨了 miRNA 基因中的遗传变异与冠心病易感性之间的关系。本综述重点介绍了近期为确定 miRNA 基因多态性与冠心病进展和易感性之间的关系而开展的研究工作。这些研究可为根据个体的遗传特征制定个性化的冠心病预防和治疗策略铺平道路。

引用次数: 0

Nanomaterials in point-of-care diagnostics: Bridging the gap between laboratory and clinical practice 护理点诊断中的纳米材料：弥合实验室与临床实践之间的差距

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155685

Madhan Jeyaraman , Naveen Jeyaraman , Swaminathan Ramasubramanian , Sangeetha Balaji , Karthikeyan.P. Iyengar , Vijay Kumar Jain , Ramya Lakshmi Rajendran , Prakash Gangadaran

The integration of nanomaterials into biosensing technologies represents a paradigm shift in medical diagnostics and environmental monitoring, marking a significant advancement in the field. This comprehensive review examines the role of nanomaterials, such as gold nanoparticles, carbon nanotubes, graphene, and quantum dots, in enhancing the performance of biosensors. These nanomaterials contribute unique physical and chemical properties, including exceptional electrical, optical, and thermal conductivities, which significantly improve the sensitivity, specificity, and versatility of biosensors. The review provides an in-depth analysis of the mechanisms by which these nanomaterials enhance biosensor functionality, including increased surface-to-volume ratio, improved electron transfer rates, and enhanced signal transduction. The practical applications of these advanced biosensors are explored across various domains, including oncology, infectious diseases, diabetes management, cardiovascular health, and neurodegenerative conditions, emphasizing their role in early disease detection, real-time health monitoring, and personalized medicine. Furthermore, the review addresses the critical challenges and limitations facing the field, such as biocompatibility, biofouling, stability, and integration into existing healthcare systems. Strategies to overcome these challenges, including advanced material engineering and novel fabrication techniques, are discussed. The future of nanomaterial-based biosensors is envisioned through the lens of emerging trends and technological innovations. The integration with microfluidics, artificial intelligence, and wearable technology is highlighted as a path toward more personalized, efficient, and accessible healthcare solutions. This review underscores the transformative impact of nanomaterials in biosensing, projecting a future where these advanced technologies play a pivotal role in reshaping diagnostics, patient care, and environmental monitoring, thereby significantly enhancing healthcare and public health outcomes.

将纳米材料融入生物传感技术代表着医学诊断和环境监测领域的范式转变，标志着该领域的重大进展。本综述探讨了金纳米粒子、碳纳米管、石墨烯和量子点等纳米材料在提高生物传感器性能方面的作用。这些纳米材料具有独特的物理和化学特性，包括优异的电导率、光导率和热导率，可显著提高生物传感器的灵敏度、特异性和多功能性。综述深入分析了这些纳米材料增强生物传感器功能的机制，包括提高表面体积比、改善电子传输速率和增强信号传导。文章探讨了这些先进生物传感器在各个领域的实际应用，包括肿瘤学、传染病、糖尿病管理、心血管健康和神经退行性疾病，强调了它们在早期疾病检测、实时健康监测和个性化医疗中的作用。此外，该综述还探讨了该领域面临的重大挑战和限制，如生物兼容性、生物污染、稳定性以及与现有医疗系统的整合。讨论了克服这些挑战的策略，包括先进的材料工程和新型制造技术。从新兴趋势和技术创新的角度展望了基于纳米材料的生物传感器的未来。重点介绍了与微流控、人工智能和可穿戴技术的整合，认为这是实现更个性化、更高效和更便捷的医疗解决方案的途径。这篇综述强调了纳米材料在生物传感方面的变革性影响，预测了这些先进技术在重塑诊断、病人护理和环境监测方面发挥关键作用的未来，从而显著提高医疗保健和公共卫生成果。

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引用次数: 0

Targeting the lung tumor microenvironment by phytochemicals and their nanoformulations 利用植物化学物质及其纳米制剂靶向肺部肿瘤微环境

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155679

Safia Obaidur Rab , Farag M.A. Altalbawy , Muktesh Chandra , I.A. Ariffin , Parjinder Kaur , Gulshan Rathore , Jasur Rizaev , Farah Aloraibi , Maryam Ali Najeeb , Munthir Abdulwahid Abdulhussain , Ahmed Hussein Zwamel

Lung malignancies are among the most prevalent and foremost causes of tumor-related deaths. Despite significant advancements in the understanding and management of lung cancer, resistance to traditional treatments remains a significant challenge. Understanding and targeting tumor microenvironment (TME) have attracted interest in the recent decade for eliminating various solid tumors. The lung TME has a crucial position in tumor expansion and therapy failure, driving it an engaging target for novel medicinal interventions. Plant-derived products offer a promising avenue for targeting TME due to their diverse chemical structures and biological activities. However, their clinical use is hindered by insufficient bioavailability and also possible systemic toxicity. The use of nanoparticles as delivery vehicles for natural products can overcome these challenges and enhance their therapeutic efficacy. This review article explores the potential of plant-derived products as medicinal agents for targeting lung TME. We provide an outline of the present knowledge of lung TME and explain the mechanisms by which plant-derived products can modulate key components of this microenvironment. The promising impacts and properties of nanoparticles for the delivery of these derivatives into lung tumors will also be discussed. We also review the preclinical and clinical findings for supporting the usefulness of these agents in targeting lung TME. Additionally, we highlight the challenges and forthcoming trends in the development of plant-derived products as targeted therapies for lung cancer, with a particular focus on combination therapies.

肺部恶性肿瘤是最常见和最主要的肿瘤相关死亡原因之一。尽管对肺癌的认识和治疗取得了重大进展，但对传统治疗方法的耐药性仍然是一项重大挑战。近十年来，对肿瘤微环境（TME）的了解和靶向治疗引起了人们对消除各种实体瘤的兴趣。肺部肿瘤微环境在肿瘤扩张和治疗失败中占据重要地位，因此成为新型药物干预的目标。植物提取物具有多样的化学结构和生物活性，为靶向 TME 提供了一条前景广阔的途径。然而，生物利用度不足以及可能的全身毒性阻碍了它们的临床应用。使用纳米颗粒作为天然产品的递送载体可以克服这些挑战并提高其疗效。这篇综述文章探讨了植物提取物作为靶向肺TME的药剂的潜力。我们概述了目前对肺TME的认识，并解释了植物提取物调节这一微环境关键成分的机制。此外，我们还将讨论将这些衍生物输送到肺部肿瘤的纳米颗粒的前景和特性。我们还将回顾临床前和临床研究结果，以支持这些制剂在靶向肺TME方面的有用性。此外，我们还强调了将植物衍生产品作为肺癌靶向疗法开发所面临的挑战和即将出现的趋势，并特别关注联合疗法。

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引用次数: 0

PGP9.5 expression in human tumors: A tissue microarray study on 13,920 tumors from 120 different tumor entities 人类肿瘤中 PGP9.5 的表达：对来自 120 个不同肿瘤实体的 13 920 个肿瘤进行的组织芯片研究。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155676

Sekander Scherzai , Maximilian Lennartz , Frank Jacobsen , Florian Viehweger , David Dum , Anne Menz , Ria Schlichter , Andrea Hinsch , Doris Höflmayer , Claudia Hube-Magg , Christoph Fraune , Christian Bernreuther , Patrick Lebok , Sören Weidemann , Guido Sauter , Till S. Clauditz , Till Krech , Andreas H. Marx , Ronald Simon , Stefan Steurer , Sarah Minner

The protein gene product 9.5 (PGP9.5), also termed ubiquitin C-terminal hydrolase L1 (UCH-L1) is an important component of the ubiquitination/deubiquitination system and plays a role in axonal transport. To comprehensively determine PGP9.5 expression in neoplastic tissues, a tissue microarray containing 13,920 samples from 120 different tumor types and subtypes was analyzed by immunohistochemistry (IHC). PGP9.5 immunostaining was found in 109 of 120 tumor categories, 87 of which contained at least one strongly positive case. PGP9.5 positivity was most seen in neuronal and neuroendocrine neoplasms (50–100 %), germ cell neoplasms (28–84 %), sarcomas and carcinosarcomas (up to 91 %), and in mesotheliomas (58–83 %). In clear cell RCC (renal cell carcinomas), strong PGP9.5 staining was associated with high ISUP (International Society of Urological Pathology) grade (p<0.0001), advanced pT stage (p=0.0003), nodal (p=0.0242) and distant metastasis (p<0.0001) as well as with a short overall, tumor specific and recurrence free survival (p≤0.0007 each). In papillary RCC, strong PGP9.5 staining was associated with high ISUP grade (p=0.009) and reduced recurrence free survival (p=0.0221). In urothelial carcinoma of the urinary bladder, high PGP9.5 expression was associated with muscle-invasion (p<0.0001). PGP9.5 immunostaining was unrelated to histological parameters for tumor aggressiveness in 295 serous high-grade ovarian carcinomas, 174 endometrioid endometrium carcinomas, 292 papillary and 89 follicular thyroid carcinomas, 405 ductal adenocarcinomas of the pancreas and in 327 gastric adenocarcinomas. In summary, our data provide a comprehensive overview of PGP9.5 expression in cancer and demonstrate positive cases in a broad range of entities. PGP9.5 overexpression is linked to patient outcome in some tumor entities (i.e., clear cell RCC) but appears to be unrelated to clinically relevant tumor characteristics in many other frequent tumor entities.

蛋白基因产物 9.5（PGP9.5）又称泛素 C 端水解酶 L1（UCH-L1），是泛素化/去泛素化系统的重要组成部分，在轴突运输中发挥作用。为了全面确定 PGP9.5 在肿瘤组织中的表达，我们通过免疫组织化学（IHC）分析了一个包含 13,920 个样本的组织芯片，这些样本来自 120 种不同的肿瘤类型和亚型。在 120 个肿瘤类别中的 109 个中发现了 PGP9.5 免疫染色，其中 87 个至少有一个强阳性病例。PGP9.5 阳性最多见于神经元和神经内分泌肿瘤（50%-100%）、生殖细胞肿瘤（28%-84%）、肉瘤和癌肉瘤（高达 91%）以及间皮瘤（58%-83%）。在透明细胞 RCC（肾细胞癌）中，PGP9.5 的强染色与 ISUP（国际泌尿病理学会）的高分级相关（p＜0.05）。

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引用次数: 0

Evaluating the diagnostic potential of SOCS3 in copper metabolism for acute myocardial infarction 评估 SOCS3 在急性心肌梗死铜代谢中的诊断潜力。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155688

Duixin Qiu, Xinrong Jia, Ye Ding, Yating Gao, Xiaodong Chen, Dan Huang

Acute myocardial infarction (AMI) represents a critical cardiovascular condition necessitating rapid and precise diagnostic strategies. This study investigates the diagnostic implications of genes involved in copper metabolism homeostasis in AMI. We identified genes related to copper metabolism and AMI from Genecards and GEO databases, conducting differential gene analysis via R software. Gene function was annotated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, while the STRING database facilitated key gene identification via topological analysis. The diagnostic value of these genes, particularly cytokine signaling 3 (SOCS3), was assessed using ROC curve analysis. SOCS3 expression was validated using in-vitro and in-vivo models, including cardiomyocyte hypoxia/reoxygenation (H/R) and rat myocardial infarction (MI) model. Further, we examined the effects of SOCS3 knockout on cell proliferation, apoptosis, and myocardial infarction severity. 77 genes were identified, with 73 showing upregulation and 4 downregulation. These genes mainly participated in pathways related to cytokine activation, inflammation regulation, and lipid metabolism. Network analysis highlighted 10 key genes, with SOCS3 exhibiting significant diagnostic potential (AUC > 0.9). Validation experiments confirmed SOCS3 overexpression in disease models, with its knockout leading to decreased apoptosis, reduced infarct size, and improved cardiac function. This study highlights the diagnostic relevance of genes associated with copper metabolism, particularly SOCS3, in AMI. These findings offer novel insights into the molecular mechanisms of AMI, supporting the development of targeted diagnostic and therapeutic strategies.

急性心肌梗死（AMI）是一种危急的心血管疾病，需要快速、精确的诊断策略。本研究探讨了铜代谢平衡相关基因对急性心肌梗死的诊断意义。我们从 Genecards 和 GEO 数据库中发现了与铜代谢和 AMI 相关的基因，并通过 R 软件进行了差异基因分析。通过基因本体（GO）和京都基因组百科全书（KEGG）富集分析对基因功能进行了注释，而 STRING 数据库则通过拓扑分析帮助识别了关键基因。利用 ROC 曲线分析评估了这些基因的诊断价值，尤其是细胞因子信号转导 3（SOCS3）。通过体外和体内模型，包括心肌细胞缺氧/再氧合（H/R）和大鼠心肌梗死（MI）模型，验证了 SOCS3 的表达。此外，我们还研究了 SOCS3 基因敲除对细胞增殖、凋亡和心肌梗死严重程度的影响。结果发现了 77 个基因，其中 73 个基因上调，4 个基因下调。这些基因主要参与细胞因子活化、炎症调节和脂质代谢相关通路。网络分析突出了 10 个关键基因，其中 SOCS3 具有显著的诊断潜力（AUC > 0.9）。验证实验证实了 SOCS3 在疾病模型中的过度表达，敲除 SOCS3 可减少细胞凋亡、缩小梗死范围并改善心脏功能。这项研究强调了铜代谢相关基因（尤其是 SOCS3）在急性心肌梗死中的诊断意义。这些发现为了解急性心肌梗死的分子机制提供了新的视角，有助于开发有针对性的诊断和治疗策略。

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引用次数: 0

Gamma-glutamyl cyclotransferase, a molecule identified from the invasive front of follicular thyroid carcinoma, is useful for differential diagnosis of follicular thyroid tumors γ-谷氨酰环基转移酶是从甲状腺滤泡癌的浸润前沿发现的一种分子，它有助于甲状腺滤泡肿瘤的鉴别诊断。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155678

Toshiyuki Mitsuhashi , Sachiko Ogasawara , Masamichi Nakayama , Reiichiro Kondo , Jun Akiba , Kenta Murotani , Takeharu Ono , Fumihiko Sato , Hirohito Umeno , Hirohisa Yano

We aimed to establish a useful molecular marker for differentiating between follicular thyroid carcinoma (FTC) and follicular adenoma (FA). RNA was extracted from the invasive front and paired tumor center tissues from three FTC cases using laser microdissection for cDNA microarray analysis, revealing high expression of gamma-glutamyl cyclotransferase (GGCT) in the invasive front. Subsequently, immunohistochemical (IHC) staining of GGCT was performed with formalin-fixed paraffin-embedded (FFPE) sections of FTC (n = 32), FA (n = 64), and follicular tumor of uncertain malignant potential (FT-UMP, n = 5). The GGCT expression score (range: 0–300) was calculated by multiplying the intensity score (0–3) and percentage of positive cells. The Ki-67 labeling index was also assessed in 20 FTC and 25 FA cases from the same cohort. The GGCT expression score was higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, P < 0.0001). With the GGCT expression score, using a cutoff value of 101.1, the differentiation between FTC and FA was possible with a sensitivity of 68.8 % and specificity of 87.5 % (AUC = 0.832). With the Ki-67 labeling index, applying a cutoff value of 4.0 %, the distinction between FTC and FA resulted in a sensitivity of 50.0 % and specificity of 80.0 % (AUC = 0.677). The GGCT expression score was positively related to the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, P = 0.0164). Therefore, GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may be indicative of its invasive and proliferative activity.

我们的目的是建立一个有用的分子标记，用于区分滤泡性甲状腺癌（FTC）和滤泡性腺瘤（FA）。我们使用激光显微切割技术从三例 FTC 患者的浸润前区和配对的肿瘤中心组织中提取了 RNA，并进行了 cDNA 微阵列分析，结果显示γ-谷氨酰环基转移酶（GGCT）在浸润前区高表达。随后，对 FTC（32 例）、FA（64 例）和恶性程度不确定的滤泡性肿瘤（FT-UMP，5 例）的福尔马林固定石蜡包埋切片进行了 GGCT 免疫组化染色。GGCT 表达评分（范围：0-300）由强度评分（0-3）和阳性细胞百分比相乘计算得出。此外，还对同组的 20 例 FTC 和 25 例 FA 进行了 Ki-67 标记指数评估。FTC的GGCT表达评分高于FA（118.5 ± 51.4 vs. 57.3 ± 34.7，P < 0.0001）。GGCT表达评分的临界值为101.1，FTC和FA的鉴别灵敏度为68.8%，特异度为87.5%（AUC = 0.832）。Ki-67标记指数的临界值为4.0%，区分FTC和FA的灵敏度为50.0%，特异度为80.0%（AUC = 0.677）。在FTC病例中，GGCT表达评分与Ki-67标记指数呈正相关。(Spearman's ρ = 0.5293，P = 0.0164）。因此，GGCT是区分FTC和FA的潜在标志物。FTC 的 GGCT 表达可能表明其具有侵袭性和增殖性。

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引用次数: 0

Regulatory mechanisms and pathological implications of CYP24A1 in Vitamin D metabolism CYP24A1 在维生素 D 代谢中的调节机制和病理影响。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155684

KL Milan, K.M. Ramkumar

CYP24A1 is a crucial gene within the cytochrome P450 superfamily, responsible for encoding the enzyme 25-hydroxyvitamin D3–24-hydroxylase. This enzyme is involved in the catabolism of 1,25-dihydroxyvitamin D3, the biologically active form of vitamin D3, by hydroxylating its side chain. Through this process, CYP24A1 tightly regulates the bioavailability and physiological impact of vitamin D3 in the body. Dysregulation of CYP24A1, particularly its overexpression, has been increasingly associated with the progression of various diseases, including cancers, autoimmune disorders, and chronic inflammatory conditions. Elevated levels of CYP24A1 can lead to excessive degradation of vitamin D3, resulting in diminished levels of this critical hormone, which is essential for calcium homeostasis, immune function, and cellular proliferation. This review explores into the structural characteristics of CYP24A1, exploring how it influences its enzymatic activity. Furthermore, it examines the expression patterns of CYP24A1 across different diseases, emphasizing the enzyme's role in disease pathology. The review also discusses the regulatory mechanisms governing CYP24A1 expression, including genetic mutations, epigenetic modifications, and metabolite-mediated regulation. By understanding these mechanisms, the review provides insight into the potential therapeutic strategies that could target CYP24A1, aiming to alleviate its overexpression and restore vitamin D3 balance in disease states.

CYP24A1 是细胞色素 P450 超家族中的一个重要基因，负责编码 25- 羟维生素 D3-24- 羟化酶。这种酶通过羟化 1,25-二羟维生素 D3 的侧链，参与 1,25-二羟维生素 D3（维生素 D3 的生物活性形式）的分解代谢。通过这一过程，CYP24A1 严格调节体内维生素 D3 的生物利用率和生理影响。CYP24A1 的失调，尤其是其过度表达，越来越多地与癌症、自身免疫性疾病和慢性炎症等各种疾病的进展有关。CYP24A1 水平的升高会导致维生素 D3 的过度降解，从而导致这种对钙平衡、免疫功能和细胞增殖至关重要的激素水平降低。这篇综述探讨了 CYP24A1 的结构特征，探讨了它如何影响其酶活性。此外，它还研究了 CYP24A1 在不同疾病中的表达模式，强调了该酶在疾病病理中的作用。综述还讨论了 CYP24A1 表达的调控机制，包括基因突变、表观遗传修饰和代谢物介导的调控。通过了解这些机制，综述深入探讨了针对 CYP24A1 的潜在治疗策略，旨在缓解其过度表达，恢复疾病状态下的维生素 D3 平衡。

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引用次数: 0

Subclinical amyloid deposition in inflammatory bowel diseases: A two hospital study 炎症性肠病的亚临床淀粉样沉积：两家医院的研究

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155682

Yuichiro Hamamoto , Kansuke Kido , Michihiro Kawamura , Yuki Sekido , Takayuki Ogino , Hironao Yasuoka , Hideki Iijima , Tsunekazu Mizushima

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), predominantly affects young patients and leads to intestinal complications. Amyloidosis, which involves abnormal protein deposition, is a serious complication of IBD, with a low incidence. Early detection of subclinical amyloid deposits is crucial for preventing fatal outcomes; however, routine investigations are lacking. We aimed to retrospectively examine subclinical amyloid deposition in adult patients with IBD. Surgical specimens from 249 patients with IBD were collected from the databases of two hospitals. The specimens were subjected to staining and immunohistochemistry, and clinical information was collected simultaneously. The amyloid positivity rate was 0.8 % in CD (1/131) and 0 % in UC (0/118) based on Congo red staining. The patient with amyloid deposits was a female in her 80 s who lacked a family history of amyloidosis. The subtype was amyloid A. Clinical history revealed intestinal resection in her 30 s and subsequent abdominal symptoms. To the best of our knowledge, this is the first study to collect >100 surgically examined specimens from adults with CD or UC. In older patients with a long and complex clinical course, aggressive analysis of amyloids would be better.

炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），主要影响年轻患者并导致肠道并发症。淀粉样变性涉及异常蛋白质沉积，是 IBD 的一种严重并发症，但发病率较低。早期发现亚临床淀粉样变性沉积对预防致命后果至关重要，但目前缺乏常规检查。我们的目的是回顾性研究成年 IBD 患者的亚临床淀粉样沉积。我们从两家医院的数据库中收集了 249 名 IBD 患者的手术标本。对标本进行染色和免疫组化，并同时收集临床信息。根据刚果红染色，CD（1/131）和 UC（0/118）的淀粉样蛋白阳性率分别为 0.8%和 0%。淀粉样蛋白沉积患者是一名80多岁的女性，没有淀粉样变性家族史。亚型为淀粉样蛋白A。临床病史显示，她在30多岁时进行过肠道切除术，随后出现腹部症状。据我们所知，这是第一项从患有 CD 或 UC 的成人中收集超过 100 份手术检查标本的研究。对于临床病程长且复杂的老年患者，积极分析淀粉样蛋白会更好。

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引用次数: 0

Nonsense-mediated mRNA decay: Physiological significance, mechanistic insights and future implications 有义介导的 mRNA 衰变：生理意义、机理认识和未来影响

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice

Pub Date : 2024-10-28 DOI: 10.1016/j.prp.2024.155677

Asish Kumar Patro, Gagan Kumar Panigrahi, Sanjoy Majumder, Rutupurna Das, Annapurna Sahoo

Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades premature aberrant transcripts and importantly, it also takes part in gene expression regulation by regulating the endogenous transcripts. NMD distinguishes aberrant and non-aberrant transcript by looking after the NMD signatures such as long 3′ UTR. NMD modulates cellular surveillance and eliminates the plausible synthesis of truncated proteins as because if the aberrant mRNA escapes the surveillance pathway it can lead to potential negative phenotype resulting in genetic diseases. NMD involves multiple proteins and any alteration or mutation within these proteins results in various pathophysiological consequences. NMD plays a complex role in cancer, it can either aggravate or downregulates the tumour. Some tumours agitate NMD to deteriorate mRNAs encoding tumour suppressor proteins, stress response proteins and neoantigens. In other case, tumours suppress the NMD to encourage the expression of oncoproteins for tumour growth and survival. In this review, we have shed light on the core and associated proteins of NMD, further summarized the mechanism of the NMD pathway and also described the implications of mutations in NMD factors resulting in severe pathological conditions including neurodevelopmental disorder, effects on male sterility and cancer. Understanding the complexities of NMD regulation and its interaction with other cellular processes can lead to the development of new interventions for various diseases. This review summarizes the current understanding of NMD and its role in controlling various cellular processes in both development and disease.

无义介导的 mRNA 降解（NMD）是一种质量控制机制，可检测和降解过早出现的异常转录本，重要的是，它还通过调节内源转录本参与基因表达调控。NMD 通过观察 NMD 标志（如长 3′ UTR）来区分异常和非异常转录本。NMD 可调节细胞监控，消除似是而非的截短蛋白合成，因为如果异常 mRNA 逃过监控途径，就会导致潜在的负面表型，导致遗传疾病。NMD 涉及多种蛋白质，这些蛋白质的任何改变或突变都会导致各种病理生理后果。NMD 在癌症中扮演着复杂的角色，它可以加重或减轻肿瘤的病情。一些肿瘤会刺激 NMD 使编码肿瘤抑制蛋白、应激反应蛋白和新抗原的 mRNA 发生恶化。在另一种情况下，肿瘤会抑制 NMD 以促进肿瘤生长和存活所需的癌蛋白的表达。在这篇综述中，我们阐明了 NMD 的核心蛋白和相关蛋白，进一步总结了 NMD 途径的机制，还描述了 NMD 因子突变导致神经发育障碍、影响男性不育和癌症等严重病理状况的影响。了解 NMD 调节的复杂性及其与其他细胞过程的相互作用，有助于开发治疗各种疾病的新干预措施。本综述总结了目前对 NMD 及其在发育和疾病过程中控制各种细胞过程的作用的理解。

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引用次数: 0