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Next generation DNA sequencing data analysis and its application in clinical genomics 下一代DNA测序数据分析及其在临床基因组学中的应用
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-30 DOI: 10.1016/j.prp.2025.156280
Abhijit Beura , Gowrang Kasaba Manjunath , Shweta Mahalingam , Mangesh Sudhakar Rajguru , Tikam Chand Dakal , Abhishek Kumar
Next-generation sequencing (NGS) has transformed genomics by enabling rapid, high-throughput analysis of DNA and RNA, driving significant progress across multiple fields, such as cancer research, rare disease diagnosis, and personalized medicine. This review discusses the wide-ranging applications of NGS, particularly in identifying genetic variants that guide the development of targeted therapies, improving patient outcomes. The NGS workflow involves crucial steps including data quality control, sequence alignment, and variant calling, supported by both open-source and commercial tools. Cloud-based platforms have further streamlined the storage, management, and processing of the vast datasets generated by NGS technologies. As NGS continues to evolve, ethical challenges, especially concerning genomic data privacy and informed consent, remain critical considerations. Looking ahead, the integration of multi-omics data and the advent of single-cell sequencing hold the potential to deepen our understanding of complex biological processes. Essential databases like dbSNP, COSMIC, and The Cancer Genome Atlas are key resources for interpreting NGS findings and their clinical significance. By effectively utilizing these tools and datasets, researchers can generate new genetic insights with far-reaching implications for advancing human health and understanding disease mechanisms.
下一代测序(NGS)通过实现DNA和RNA的快速、高通量分析,改变了基因组学,推动了癌症研究、罕见疾病诊断和个性化医疗等多个领域的重大进展。这篇综述讨论了NGS的广泛应用,特别是在识别遗传变异,指导靶向治疗的发展,改善患者预后方面。NGS工作流程包括关键步骤,包括数据质量控制、序列比对和变体调用,这些都得到了开源和商业工具的支持。基于云的平台进一步简化了NGS技术产生的大量数据集的存储、管理和处理。随着NGS的不断发展,伦理挑战,特别是关于基因组数据隐私和知情同意,仍然是关键的考虑因素。展望未来,多组学数据的整合和单细胞测序的出现有可能加深我们对复杂生物过程的理解。基本数据库如dbSNP、COSMIC和The Cancer Genome Atlas是解释NGS发现及其临床意义的关键资源。通过有效地利用这些工具和数据集,研究人员可以产生新的遗传见解,对促进人类健康和理解疾病机制具有深远的意义。
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引用次数: 0
Chuanxing Qingfei Syrup ameliorates acute lung injury by suppressing BCL10 expression and blocking the IKK/IκBα/NF-κB pathway 川星清肺糖浆通过抑制BCL10表达和阻断IKK/ i -κB α/NF-κB通路改善急性肺损伤
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI: 10.1016/j.prp.2025.156273
Yuanyuan Song , Heng Li , Yanyun Zhao , Chen Cheng , Weiwei Zhang , Yingying Sun , Taiyu Jin

Background

Acute lung injury (ALI) is a potentially lethal condition with a considerable mortality rate. This study aims to determine the protective effect of Chuanxing Qingfei Syrup (CQS) against ALI.

Methods

An ALI model was constructed by dropping lipopolysaccharide (LPS) into the trachea of mice, and mice were treated with low, medium, and high doses of CQS to evaluate the therapeutic effect of CQS. LPS-treated A549 cells were used to construct an in vitro ALI model, and low, medium, and high doses of CQS were used to treat A549 cells. The cytotoxicity and therapeutic efficacy of CQS were verified. Bioinformatic analysis was employed to predict the downstream targets of CQS. BCL10 expression in mouse lung tissues and A549 cells was detected. The phosphorylation level of IKKβ, IκBα, and NF-κB p65, and the nuclear translocation of NF-κB p65 were measured. BCL10 overexpression and treatment with the NF-κB pathway inhibitor PDTC were performed to explore their effects on A549 cell injury. Intranasal instillation of overexpressed BCL10 adeno-associated virus was performed to observe its effect on ALI mice.

Results

CQS effectively alleviated the infiltration of inflammatory cells, reduced levels of inflammatory factors, inhibited apoptosis, and alleviated lung edema in mice. CQS inhibited apoptosis in A549 cells. CQS inhibited BCL10, and BCL10 activated the IKK/IκBα/NF-κB pathway. Overexpression of BCL10 aggravated A549 cell injury and pathological changes in ALI mice. PDTC treatment mitigated LPS-induced injury in A549 cells overexpressing BCL10.

Conclusion

CQS inhibits ALI progression by targeting BCL10 and suppressing the IKK/IκBα/NF-κB pathway.
背景:急性肺损伤(ALI)是一种具有潜在致命性的疾病,死亡率相当高。本研究旨在探讨川兴清肺糖浆(CQS)对ALI的保护作用。方法将脂多糖(LPS)滴入小鼠气管,建立小鼠三ALI模型,并分别给予小鼠低、中、高剂量CQS,评价CQS对小鼠的治疗作用。采用lps处理的A549细胞构建体外ALI模型,并采用低、中、高剂量CQS处理A549细胞。验证了CQS的细胞毒性和治疗效果。采用生物信息学方法预测CQS的下游靶点。检测BCL10在小鼠肺组织和A549细胞中的表达。检测IKKβ、i -κB α、NF-κB p65磷酸化水平及NF-κB p65核易位。通过对BCL10过表达和NF-κB通路抑制剂PDTC的处理,探讨其对A549细胞损伤的影响。通过鼻内注射过表达的BCL10腺相关病毒,观察其对ALI小鼠的影响。结果scqs能有效减轻小鼠炎性细胞浸润,降低炎性因子水平,抑制细胞凋亡,减轻肺水肿。CQS抑制A549细胞凋亡。CQS抑制BCL10, BCL10激活IKK/ i -κB α/NF-κB通路。BCL10过表达加重了ALI小鼠A549细胞损伤及病理改变。PDTC处理可减轻lps诱导的过表达BCL10的A549细胞损伤。结论cqs通过靶向BCL10、抑制IKK/ i -κB α/NF-κB通路抑制ALI进展。
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引用次数: 0
Integrating transcriptomics and machine learning to predict ferroptosis-related genes and analyzing the role of GOT1 in gastric cancer progression 整合转录组学和机器学习预测嗜铁相关基因并分析GOT1在胃癌进展中的作用。
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1016/j.prp.2025.156252
Xiao-Ling Wu , Li-Ping Lei , Shu-Rui Wu, Mei-Yan Chen, Yu-Qin Zhang, Yu-Ka Fu, Qiong-Dan Kang, Shan-Ti Lin, Pei Li, Zhang-Xing Chen
<div><h3>Background</h3><div>Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Despite advances in treatment, the prognosis for advanced GC remains poor, highlighting the need for new therapeutic targets. Ferroptosis, a form of programmed cell death characterized by iron-dependent lipid peroxidation, has emerged as a potential pathway for cancer therapy. This study aims to identify ferroptosis-related genes in GC using transcriptomics and machine learning, and to validate the role of one key gene, Glutamic-Oxaloacetic Transaminase 1 (GOT1), in GC progression.</div></div><div><h3>Methods</h3><div>The Sangerbox platform was employed to analyze differentially expressed genes between GC tissues and adjacent non-cancerous tissues in the GSE184336 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify co-expressed gene modules from the GSE184336 dataset and their associations with phenotypes. Support Vector Machine (SVM) and Random Forest (RF) regression algorithms were applied to screen for core target genes. Quantitative Real-Time PCR (qRT-PCR) was used to analyze mRNA expression, while western blotting and immunohistochemistry (IHC) assays were used to determine protein expression. Cell proliferation was assessed using a 5-Ethynyl-2’-deoxyuridine assay, and cell migration was analyzed using a Transwell assay. Flow cytometry was used to quantify cell death. Fluorometric and colorimetric assays were performed to analyze Reactive Oxygen Species (ROS) and Fe<sup>2 +</sup> levels, respectively. A xenograft mouse model was used to evaluate the impact of GOT1 overexpression on tumor formation <em>in vivo</em>. Haematoxylin and eosin (HE) staining was used to analyze the pathological conditions of tumors.</div></div><div><h3>Results</h3><div>The analysis of the GSE184336 dataset identified 2297 dysregulated genes in GC tissues compared to adjacent non-cancerous tissues. WGCNA revealed strong correlations between gene significance and module membership in the “green,” “ivory,” and “lightsteelblue1” modules, encompassing 350 genes. Subsequent analysis identified 14 intersection genes among the 2297 dysregulated genes in GC tissues, the 350 genes from WGCNA, and the 1467 genes related to ferroptosis. Machine learning algorithms and protein-protein interaction analysis identified IDH2, BGN, IGFBP7, and GOT1 as key genes. GOT1 expression was downregulated in GC tissues with the lowest error value. Overexpression of GOT1 inhibited GC cell proliferation, migration, and induced ferroptosis, whereas these effects were reversed by treatment with Fer-1. Further, GOT1 overexpression suppressed the malignant phenotype of GC cells in vivo.</div></div><div><h3>Conclusion</h3><div>This study identified several ferroptosis-related genes in GC, with GOT1 being a critical regulator. Overexpression of GOT1 significantly inhibited GC cell proliferation and migration, and induced ferroptosis. These findings sugges
背景:胃癌(GC)是世界范围内癌症相关死亡的主要原因之一。尽管治疗取得了进展,但晚期胃癌的预后仍然很差,需要新的治疗靶点。铁凋亡是一种以铁依赖性脂质过氧化为特征的程序性细胞死亡形式,已成为癌症治疗的潜在途径。本研究旨在利用转录组学和机器学习技术鉴定GC中凋亡相关基因,并验证其中一个关键基因谷草转氨酶1 (GOT1)在GC进展中的作用。方法:采用Sangerbox平台分析GSE184336数据集中胃癌组织与癌旁非癌组织之间的差异表达基因。加权基因共表达网络分析(Weighted Gene Co-expression Network Analysis, WGCNA)用于鉴定GSE184336数据集中的共表达基因模块及其与表型的关联。采用支持向量机(SVM)和随机森林(RF)回归算法筛选核心靶基因。采用实时荧光定量PCR (qRT-PCR)分析mRNA表达,western blotting和免疫组化(IHC)检测蛋白表达。使用5-乙基-2'-脱氧尿苷法评估细胞增殖,使用Transwell法分析细胞迁移。流式细胞术定量细胞死亡。采用荧光法和比色法分别分析活性氧(ROS)和Fe2 +水平。采用异种移植小鼠模型来评估GOT1过表达对体内肿瘤形成的影响。采用苏木精和伊红(HE)染色分析肿瘤的病理情况。结果:对GSE184336数据集的分析发现,与邻近非癌组织相比,GC组织中存在2297个异常基因。WGCNA揭示了基因重要性与“绿色”、“象牙色”和“光钢蓝”模块成员之间的强相关性,这些模块包含350个基因。随后的分析确定了GC组织中2297个失调基因中的14个交叉基因,WGCNA中的350个基因,以及与铁下垂相关的1467个基因。机器学习算法和蛋白质相互作用分析鉴定出IDH2、BGN、IGFBP7和GOT1是关键基因。GC组织中GOT1表达下调,误差值最低。GOT1过表达抑制GC细胞增殖、迁移并诱导铁下垂,而这些作用被fer1处理逆转。此外,GOT1过表达在体内抑制GC细胞的恶性表型。结论:本研究在GC中发现了几个与嗜铁有关的基因,其中GOT1是一个关键的调控因子。过表达GOT1显著抑制GC细胞增殖和迁移,诱导铁下垂。这些发现表明GOT1可以作为GC治疗的潜在治疗靶点。
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引用次数: 0
U2AF2 drives malignant progression and chemo-resistance in hepatocellular carcinoma through cooperating with SRSF1 to modulate CCND1 splice-variant expression U2AF2通过与SRSF1合作调节CCND1剪接变异体的表达,驱动肝癌的恶性进展和化疗耐药
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1016/j.prp.2025.156272
Peng Luo , Shijie Dai , Xingyuan Xu , Gaoyu Liu, Fulong Wang, Jialun Li, Qin Xiong, Yang Wang, Chunmeng Shi
Hepatocellular carcinoma (HCC) is a common malignancy with high risk of recurrence and metastasis. Growing evidences reveal that aberrant mRNA splicing represents a crucial molecular characteristic of cancer, which produces numerous and complex transcript variants to drive cancer development and progression. Here, we identified the splicing factor U2AF2 as a promising oncogenic biomarker in HCC, and subsequently explored its biological role and mechanism. Through bioinformatics analysis and clinical verification, U2AF2 was found to be significantly elevated in HCC, showing a strong correlation with the pathological grade and patient outcomes. Subsequent investigations demonstrated that U2AF2 promoted HCC growth and metastasis both in vitro and in vivo. Mechanically, U2AF2 exerted its oncogenic functions by cooperating with SRSF1 to bind to the pre-mRNA of CCND1(Cyclin D1) and facilitate the generation of CCND1b isoform. Moreover, U2AF2 could potentially be utilized for the prediction of chemo-responsiveness. Its depletion sensitized HCC cells to Doxorubicin, a first-line chemotherapy agent for advanced HCC patients. Altogether, this study deepens our understanding of U2AF2 in mRNA splicing and provides a potential therapeutic target for HCC.
肝细胞癌(HCC)是一种常见的恶性肿瘤,具有较高的复发和转移风险。越来越多的证据表明,异常的mRNA剪接是癌症的一个重要分子特征,它产生了大量复杂的转录变体,驱动癌症的发生和进展。本研究中,我们确定了剪接因子U2AF2作为HCC中一个有前景的致癌生物标志物,并随后探讨了其生物学作用和机制。通过生物信息学分析和临床验证,发现U2AF2在HCC中显著升高,与病理分级和患者预后有很强的相关性。随后的研究表明,U2AF2在体外和体内都促进了HCC的生长和转移。机械上,U2AF2通过与SRSF1合作,结合CCND1的前mrna (Cyclin D1),促进CCND1b亚型的产生,发挥其致癌功能。此外,U2AF2可以潜在地用于预测化学反应性。它的耗竭使HCC细胞对阿霉素敏感,阿霉素是晚期HCC患者的一线化疗药物。总之,本研究加深了我们对U2AF2在mRNA剪接中的理解,并为HCC提供了一个潜在的治疗靶点。
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引用次数: 0
Mechanistic insights into plant-derived natural compounds for the treatment of skin cancer: Targeting molecular signaling for therapeutic intervention 植物来源的天然化合物治疗皮肤癌的机制:靶向分子信号治疗干预。
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.prp.2025.156277
Ashutosh Pathak , G. Surendra , Sathvik Belagodu Sridhar , Patibandla Jahnavi , Jeetendra Kumar Gupta , P. Balaji , N. Juniorsundresh , Konatham Teja Kumar Reddy , Abdul Ajeed Mohathasim Billah , Karthickeyan Krishnan
Skin cancer, a prevalent global cancer, is primarily caused by chronic environmental exposures and cellular signaling pathway deregulation. Traditional therapies like radiation, chemotherapy, and surgery face toxicity, resistance, and recurrence issues. Natural compounds, with their diverse biological activity and minimal side effects, are increasingly recognized as potential therapeutic agents. This review explores the potential of natural compounds in treating skin cancer by modifying key molecular signaling pathways, including MAPK/ERK, PI3K/Akt, NF-κB, STAT3, and Wnt/β-catenin. Curcumin, resveratrol, quercetin, epigallocatechin gallate, and genistein are natural substances known to have potent anticancer effects by inhibiting cell proliferation, promoting apoptosis, and preventing metastasis. These substances regulate inflammation, prevent angiogenesis, enhance drug effectiveness, combat multidrug resistance, and have low toxicity to healthy skin cells, indicating potential therapeutic use. Additionally, their compatibility with current chemotherapeutic drugs underscores their significant role in combating drug resistance. The review underscores the importance of understanding the molecular mechanisms underlying phytochemicals' anticancer properties to facilitate their integration into modern treatment methods. Future initiatives should focus on clinical validation, increasing bioavailability, and targeting administration schemes to maximize the therapeutic potential of natural chemicals against skin cancer.
皮肤癌是一种全球普遍存在的癌症,主要是由慢性环境暴露和细胞信号通路失调引起的。传统的治疗方法,如放疗、化疗和手术,面临着毒性、耐药性和复发问题。天然化合物由于其多样的生物活性和最小的副作用,越来越被认为是潜在的治疗药物。本文通过对MAPK/ERK、PI3K/Akt、NF-κB、STAT3和Wnt/β-catenin等关键分子信号通路的调控,探讨了天然化合物治疗皮肤癌的潜力。姜黄素、白藜芦醇、槲皮素、没食子儿茶素没食子酸酯和染料木素是已知的天然物质,通过抑制细胞增殖、促进细胞凋亡和防止转移而具有有效的抗癌作用。这些物质调节炎症,防止血管生成,增强药物有效性,对抗多药耐药,并且对健康皮肤细胞毒性低,表明潜在的治疗用途。此外,它们与当前化疗药物的相容性强调了它们在对抗耐药性方面的重要作用。该综述强调了了解植物化学物质抗癌特性的分子机制的重要性,以促进它们与现代治疗方法的结合。未来的举措应侧重于临床验证、提高生物利用度和靶向给药方案,以最大限度地发挥天然化学物质对皮肤癌的治疗潜力。
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引用次数: 0
Automated spatial analysis reveals proximity of human leukocyte antigen class I-positive tumor cells and CD8-positive cells of the tumor microenvironment in stage I seminoma 自动空间分析揭示了I期精原细胞瘤中人类白细胞抗原I类阳性肿瘤细胞和cd8阳性肿瘤微环境细胞的接近性。
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1016/j.prp.2025.156270
Takuto Ogasawara , Terufumi Kubo , Kenta Sasaki , Naoki Shijubou , Rena Morita , Kenji Murata , Kohei Hashimoto , Tomohide Tsukahara , Hiroko Asanuma , Toshihiko Torigoe , Reiko Watanabe , Naoya Masumori , Yoshihiko Hirohashi

Background

The testis is an immune-privileged organ due to its lack of functional human leukocyte antigen (HLA) class I expression. However, the expression status of HLA class I in testicular seminoma, which is characterized histologically by lymphocytic infiltration, remains unclear.

Materials and methods

We performed immunohistochemistry to evaluate HLA class I expression and its spatial relationship with CD8-positive cells in 20 cases of stage I seminoma. Each specimen was scored manually and further analyzed using the HALO image analysis platform.

Results

Manual scoring and HALO analysis showed 80 % concordance. HLA class I expression was positive in 13 cases (65 %). Tumors were classified into three categories based on the expression levels. The number of infiltrating CD8-positive cells was significantly correlated with HLA class I expression. Spatial analysis revealed that tumors with higher HLA class I expression had shorter distances between HLA class I–positive tumor cells and CD8-positive cells.

Conclusion

Seminoma cells expressing HLA class I tended to be located in close proximity to CD8-positive T cells, suggesting a spatial relationship that might influence the tumor immune microenvironment.
背景:由于缺乏功能性人类白细胞抗原(HLA) I类表达,睾丸是一种免疫特权器官。然而,HLA I类在以淋巴细胞浸润为组织学特征的睾丸精原细胞瘤中的表达状况尚不清楚。材料和方法:应用免疫组织化学方法评价20例I期精原细胞瘤患者HLA I类表达及其与cd8阳性细胞的空间关系。每个标本手工评分,并使用HALO图像分析平台进一步分析。结果:手工评分与HALO分析的符合率为 %。HLA I类阳性13例(65 %)。根据表达水平将肿瘤分为三类。cd8阳性细胞浸润数与HLA I类表达显著相关。空间分析显示,HLA I类表达较高的肿瘤,HLA I类阳性肿瘤细胞与cd8阳性细胞之间的距离较短。结论:表达HLA I类的精原细胞瘤细胞倾向于靠近cd8阳性T细胞,可能存在影响肿瘤免疫微环境的空间关系。
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引用次数: 0
PTEN mutation status in uterine carcinosarcomas: A comprehensive overview and a new diagnostic approach PTEN在子宫癌肉瘤中的突变状态:一个全面的概述和新的诊断方法
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-11-05 DOI: 10.1016/j.prp.2025.156278
Maccio Livia , Bragantini Emma , Piermattei Alessia , Santoro Angela , Zannoni Gian Franco
Uterine carcinosarcomas (UCS), also known as malignant mixed Müllerian tumors, are rare and aggressive neoplasms characterized by the coexistence of carcinomatous (epithelial) and sarcomatous (mesenchymal) components. PTEN (Phosphatase and Tensin Homolog) mutations, a hallmark of endometrioid-type carcinomas, play a significant role in the pathogenesis and histological presentation of a subset of uterine carcinosarcomas, contributing to their aggressive behavior and poor prognosis. This overview synthesizes the current understanding of PTEN mutations in carcinosarcomas and their implications for clinical management and therapy. A new approach based on morphological, immunohistochemical, and molecular characteristics is proposed.
子宫癌肉瘤(UCS),又称恶性混合性勒氏瘤,是一种罕见的侵袭性肿瘤,其特征是癌(上皮)和肉瘤(间充质)成分共存。PTEN (Phosphatase and Tensin Homolog)突变是子宫内膜样癌的一个标志,在子宫癌肉瘤的发病机制和组织学表现中起重要作用,导致其侵袭性行为和不良预后。本综述综合了目前对癌肉瘤中PTEN突变的理解及其对临床管理和治疗的意义。提出了一种基于形态学、免疫组织化学和分子特征的新方法。
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引用次数: 0
Role of C-reactive protein in cervical intraepithelial neoplasia/cancer c反应蛋白在宫颈上皮内瘤变/癌中的作用
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-19 DOI: 10.1016/j.prp.2025.156274
Adriana Pedreañez , Yenddy Carrero , Renata Vargas , Juan P.Hernández Fonseca , Jesús Mosquera
Cervical cancer is one of the most common malignancies in women. This pathology originates from the progression of cervical intraepithelial neoplasia (CIN), induced by high-risk human papillomavirus (HPV) infection. During CIN, an inflammatory process characterized by immune system activation and increased levels of C-reactive protein (CRP) occurs. This protein, generally an indicator of inflammatory processes, also has functions that can influence the pathogenesis of several diseases. This review summarizes the current published literature (searched on Pubmed, EMBASE and Web of Science) regarding the factors that affect pathogenesis of cervical intraepithelial neoplasia/cancer mediated by CRP searched up to 2025. This review highlights the events present in CIN/cancer where CRP may be involved. CRP may induce progression of CIN to cervical cancer through its action on its lectin-like receptor oxidized low-density lipoprotein receptor-1 (LOX-1) and influence events involving complement activation, immune system activation, apoptosis induction, oxidative stress, and modulation of HPV biology.
子宫颈癌是女性最常见的恶性肿瘤之一。这种病理起源于宫颈上皮内瘤变(CIN)的进展,由高危人乳头瘤病毒(HPV)感染引起。在CIN期间,以免疫系统激活和c反应蛋白(CRP)水平升高为特征的炎症过程发生。这种蛋白质通常是炎症过程的指示器,也具有影响几种疾病发病机制的功能。本综述总结了目前已发表的文献(检索Pubmed、EMBASE和Web of Science),关于CRP介导的宫颈上皮内瘤变/癌发病机制的影响因素,检索至2025年。这篇综述强调了在CIN/癌症中CRP可能参与的事件。CRP可能通过其对凝集素样受体氧化低密度脂蛋白受体-1 (LOX-1)的作用诱导CIN进展为宫颈癌,并影响补体激活、免疫系统激活、细胞凋亡诱导、氧化应激和HPV生物学调节等事件。
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引用次数: 0
Should we subtype gastric intestinal metaplasia in gastric biopsies, a single institution’s experience 我们是否应该在胃活检中分型胃肠化生,单一机构的经验
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-11-01 Epub Date: 2025-08-27 DOI: 10.1016/j.prp.2025.156189
Haibo Wang , Yu Liu , Asra Froze , Zengying Wu , Jonathan D. Somma , Zhiyan Fu
Gastric intestinal metaplasia (GIM) is considered a risk factor for gastric dysplasia and adenocarcinoma. While surveillance endoscopies are often performed, particularly for incomplete GIM, the clinical value of histologic subtyping (complete, incomplete, or mixed) remains unclear. This study evaluated the progression risk of different GIM subtypes diagnosed through random gastric biopsies and their association with various clinical factors. Archived pathology data from 206 gastric biopsy cases were analyzed, including 52 negative controls, 56 complete GIM, 54 incomplete GIM, and 44 mixed GIM. Histologic slides were reviewed for subtype confirmation and other pathological changes; clinical data were extracted from medical records. Multiple linear regression was conducted for correlation analysis, and Analysis of Variance was used to compare group means. GIM was predominantly located in the antrum. Over a mean follow-up period of 52.2 months, none of the patients, including 12 under mapping surveillance, developed gastric neoplasia. Significant associations were found between Helicobacter pylori (H. pylori) and all types of GIM. H. pylori infection was also significantly associated with the extent of the GIM. Hypertension showed a trend toward significance in correlation with GIM, but no other associations were identified between GIM and demographic or clinical factors such as gender, age, smoking, diabetes mellitus, or hyperlipidemia. Our findings suggest that the routine subtyping GIM in pathology reports may not be necessary, given the lack of progression to any type of neoplasia within the follow-up period. However, the redemonstrated association between H. pylori and GIM emphasizes the importance of eradication therapy.
胃肠化生(GIM)被认为是胃发育不良和腺癌的危险因素。虽然经常进行内窥镜检查,特别是对于不完全性GIM,但组织学亚型(完全、不完全或混合)的临床价值尚不清楚。本研究评估了随机胃活检诊断的不同GIM亚型的进展风险及其与各种临床因素的关系。分析206例胃活检病例的病理资料,其中阴性对照52例,完全GIM 56例,不完全GIM 54例,混合性GIM 44例。检查组织切片以确定亚型和其他病理改变;临床资料从病历中提取。相关性分析采用多元线性回归,组均值比较采用方差分析。GIM主要位于胃窦。在平均52.2个月的随访期间,包括12名在绘图监测下的患者在内,没有患者发生胃肿瘤。幽门螺杆菌(h.p ylori)与所有类型的GIM之间存在显著相关性。幽门螺杆菌感染也与GIM的程度显著相关。高血压表现出与GIM显著相关的趋势,但没有发现GIM与人口统计学或临床因素(如性别、年龄、吸烟、糖尿病或高脂血症)之间的其他关联。我们的研究结果表明,在病理报告中常规的GIM亚型可能没有必要,因为在随访期间没有任何类型的瘤变进展。然而,重新证明幽门螺杆菌与GIM之间的联系强调了根除治疗的重要性。
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引用次数: 0
Microbiota in cancer care: Clinical prospects 微生物群在癌症治疗中的应用:临床前景
IF 3.2 4区 医学 Q2 PATHOLOGY Pub Date : 2025-11-01 Epub Date: 2025-09-16 DOI: 10.1016/j.prp.2025.156235
Peng Li-Hua , Ousman Bajinka

Background

Probiotics and microbial metabolites exhibit dual roles in cancer biology, serving as both therapeutic agents and biomarkers. Lactobacillus species inhibit pathogen-driven tumorigenesis and predict immunotherapy efficacy, yet their depletion correlates with polycystic ovary syndrome (PCOS) and gastrointestinal cancers. Conversely, expansion of specific strains, such as L. plantarum 299 v, enhances iron absorption and mitigates mucositis. Similarly, Bifidobacterium modulates gut microbiota (GM) toward tumor suppression in colorectal cancer (CRC) and improves pediatric outcomes, though paradoxically rising in refractory multiple myeloma. Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate protect against CRC via anti-inflammatory and epigenetic mechanisms, while Akkermansia muciniphila enhances immunotherapy responses in CRC and NSCLC through GM–tumor microenvironment crosstalk.

Objective

This mini review aimed to decipher the prospects of macromolecules in their role as anti cancer based on human clinical trials.

Interventions

Interventions include multi-strain probiotics, synbiotics, and dietary strategies (Mediterranean diets, fermented foods) that restore GM balance and boost SCFA production.

Limitations

Limitations persist on strain-specific variability, biomarker ambiguity, and inconsistent efficacy of probiotics in radiotherapy-induced diarrhea.

Recommendation

To address these, precision medicine approaches prioritizing strain-specific formulations, validated biomarkers, and combination therapies are advocated. Personalized nutrition and clinical tools further optimize outcomes.

Conclusion

Future research must clarify Akkermansia-TMAO interactions, SCFA epigenetic dynamics, and combinatorial regimens to harness microbiota–host crosstalk. By integrating advanced analytics and population-tailored strategies, microbiota-targeted interventions hold transformative potential in cancer prevention, therapy, and diagnostics.
益生菌和微生物代谢物在癌症生物学中具有双重作用,既是治疗剂又是生物标志物。乳酸菌物种抑制病原体驱动的肿瘤发生并预测免疫治疗效果,但它们的缺失与多囊卵巢综合征(PCOS)和胃肠道癌症有关。相反,特定菌株的扩增,如L. plantarum 299 v,可以增强铁的吸收并减轻粘膜炎。同样,双歧杆菌调节肠道微生物群(GM)对结直肠癌(CRC)的肿瘤抑制作用,并改善儿科预后,尽管在难治性多发性骨髓瘤中矛盾地增加。短链脂肪酸(SCFAs)醋酸酯、丙酸酯和丁酸酯通过抗炎和表观遗传机制预防结直肠癌,而嗜粘Akkermansia muciniphila通过转基因肿瘤微环境串扰增强结直肠癌和非小细胞肺癌的免疫治疗应答。目的在人体临床试验的基础上,探讨大分子抗癌作用的发展前景。干预措施包括多菌种益生菌、合成菌和饮食策略(地中海饮食、发酵食品),以恢复转基因平衡并促进短链脂肪酸的产生。局限性:菌株特异性变异、生物标志物不明确、益生菌治疗放疗性腹泻疗效不一致等方面的局限性依然存在。建议:为了解决这些问题,人们提倡优先考虑菌株特异性制剂、经过验证的生物标志物和联合治疗的精准医学方法。个性化营养和临床工具进一步优化结果。结论未来的研究必须明确Akkermansia-TMAO相互作用、SCFA表观遗传动力学以及利用微生物-宿主串扰的组合方案。通过整合先进的分析和针对人群的策略,针对微生物群的干预措施在癌症预防、治疗和诊断方面具有变革性的潜力。
{"title":"Microbiota in cancer care: Clinical prospects","authors":"Peng Li-Hua ,&nbsp;Ousman Bajinka","doi":"10.1016/j.prp.2025.156235","DOIUrl":"10.1016/j.prp.2025.156235","url":null,"abstract":"<div><h3>Background</h3><div>Probiotics and microbial metabolites exhibit dual roles in cancer biology, serving as both therapeutic agents and biomarkers. <em>Lactobacillus</em> species inhibit pathogen-driven tumorigenesis and predict immunotherapy efficacy, yet their depletion correlates with polycystic ovary syndrome (PCOS) and gastrointestinal cancers. Conversely, expansion of specific strains, such as <em>L. plantarum</em> 299 v, enhances iron absorption and mitigates mucositis. Similarly, <em>Bifidobacterium</em> modulates gut microbiota (GM) toward tumor suppression in colorectal cancer (CRC) and improves pediatric outcomes, though paradoxically rising in refractory multiple myeloma. Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate protect against CRC via anti-inflammatory and epigenetic mechanisms, while <em>Akkermansia muciniphila</em> enhances immunotherapy responses in CRC and NSCLC through GM–tumor microenvironment crosstalk.</div></div><div><h3>Objective</h3><div>This mini review aimed to decipher the prospects of macromolecules in their role as anti cancer based on human clinical trials.</div></div><div><h3>Interventions</h3><div>Interventions include multi-strain probiotics, synbiotics, and dietary strategies (Mediterranean diets, fermented foods) that restore GM balance and boost SCFA production.</div></div><div><h3>Limitations</h3><div>Limitations persist on strain-specific variability, biomarker ambiguity, and inconsistent efficacy of probiotics in radiotherapy-induced diarrhea.</div></div><div><h3>Recommendation</h3><div>To address these, precision medicine approaches prioritizing strain-specific formulations, validated biomarkers, and combination therapies are advocated. Personalized nutrition and clinical tools further optimize outcomes.</div></div><div><h3>Conclusion</h3><div>Future research must clarify <em>Akkermansia</em>-TMAO interactions, SCFA epigenetic dynamics, and combinatorial regimens to harness microbiota–host crosstalk. By integrating advanced analytics and population-tailored strategies, microbiota-targeted interventions hold transformative potential in cancer prevention, therapy, and diagnostics.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"275 ","pages":"Article 156235"},"PeriodicalIF":3.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Pathology, research and practice
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