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transcriptomic profiling reveals differential cellular response to copper oxide nanoparticles and polystyrene nanoplastics in perfused human placenta

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ENVIRONMENT INTERNATIONAL 2023年 177卷 108015页

作者： Chortarea, S. Gupta, G. Saarimaki, L. A. Netkueakul, W. Manser, P. Aengenheister, L. Wichser, A. Fortino, V. Wick, P. Greco, D. Buerki-Thurnherr, T. Swiss Fed Labs Mat Sci & Technol Empa Lab Particles Biol Interact CH-9014 St Gallen Switzerland Tampere Univ Fac Med & Hlth Technol Finnish Hub Dev & Validat Integrated Approaches FH Tampere Finland Luxembourg Inst Hlth LIH Dept Precis Hlth Human Biomonitoring Res Unit 1 A-BRue Thomas Edison L-1445 Strassen Luxembourg Swiss Fed Labs Mat Sci & Technol Empa Lab Adv Analyt Technol Dubendorf Switzerland Univ Eastern Finland Inst Biomed Sch Med Kuopio Finland Univ Helsinki Inst Biotechnol Helsinki Finland Empa Lerchenfeldstr 5 CH-9014 St Gallen Switzerland

The growing nanoparticulate pollution (e.g. engineered nanoparticles (NPs) or nanoplastics) has been shown to pose potential threats to human health. In particular, sensitive populations such as pregnant women and their unborn children need to be protected from harmful environmental exposures. However, developmental toxicity from prenatal exposure to pollution particles is not yet well studied despite evidence of particle accumulation in human placenta. Our study aimed to investigate how copper oxide NPs (CuO NPs;10-20 nm) and polystyrene nanoplastics (PS NPs;70 nm) impact on gene expression in ex vivo perfused human placental tissue. Whole genome microarray analysis revealed changes in global gene expression profile after 6 h of perfusion with subcytotoxic concentrations of CuO (10 & mu;g/mL) and PS NPs (25 & mu;g/mL). Pathway and gene ontology enrichment analysis of the differentially expressed genes suggested that CuO and PS NPs trigger distinct cellular response in placental tissue. While CuO NPs induced pathways related to angiogenesis, protein misfolding and heat shock responses, PS NPs affected the expression of genes related to inflammation and iron homeostasis. The observed effects on protein misfolding, cytokine signaling, and hormones were corroborated by western blot (accumulation of polyubiquitinated proteins) or qPCR analysis. Overall, the results of the present study revealed extensive and material-specific interference of CuO and PS NPs with placental gene expression from a single short-term exposure which deserves increasing attention. In addition, the placenta, which is often neglected in developmental toxicity studies, should be a key focus in the future safety assessment of NPs in pregnancy.

关键词： Nanoplastics CuO nanoparticles Placenta transcriptomic profiling Developmental toxicity pathways

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transcriptomic profiling of human granulosa cells between women with advanced maternal age with different ovarian reserve

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JOURNAL OF ASSISTED REPRODUCTION AND GENETICS 2023年第10期40卷 2427-2437页

作者： Jia, Zhi-cheng Li, Yong-qian Zhou, Bo-wen Xia, Qing-chang Wang, Pei-xuan Wang, Xiao-xuan Sun, Zhen-gao Guo, Ying Shandong Univ Tradit Chinese Med Clin Coll 1 Jinan Peoples R China Shandong Univ Tradit Chinese Med Coll Tradit Chinese Med Jinan Peoples R China Shandong Univ Tradit Chinese Med Reprod & Genet Ctr Integrat Med Affiliated Hosp Jinan Peoples R China

BackgroundAge-related diminished ovarian reserve (DOR) is not absolute. Some advanced maternal age (AMA) still have normal ovarian reserve (NOR) and often show better pregnancy outcomes. Exploring the transcriptomic profile of granulosa cells (GCs) in AMA could lead to new ideas for mitigating age-related diminished ovarian *** study aimed to analyze the transcriptomic profile of GCs in AMA with different ovarian *** total, 6273 statistically significant differential expression genes (DEGs) (|log2fc|> 1, q < 0.05) were screened from the two groups, among which 3436 genes were upregulated, and 2837 genes were downregulated in the DOR group. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the potential functions of dysregulated genes in AMA with DOR or NOR were predicted. The GO enrichment analysis revealed that the DEGs were mainly enriched in obsolete oxidation-reduction process, mitochondrion, metal ion binding, ATP binding, etc. The KEGG pathway enrichment analysis revealed that the above-mentioned DEGs were mainly enriched in ferroptosis, regulation of actin cytoskeleton, oxidative phosphorylation, etc. Meanwhile, verification of the mRNA expression levels of DEGs revealed the possible involvement of "ferroptosis" in age-related diminished ovarian *** a new clinical perspective, we presented the first data showing the transcriptomic profile in GCs between AMA with different ovarian reserve. At the same time, we identified the role of ferroptosis in the GCs of AMA, providing a new biological basis for studying ovarian aging and improving pregnancy outcomes of AMA.

关键词： transcriptomic profiling Granulosa cells Advanced maternal age Diminished ovarian reserve Ovarian aging Ferroptosis

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transcriptomic profiling of Ganoderic Acid Me-Mediated Prevention of Sendai Virus Infection

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CURRENT BIOINFORMATICS 2022年第7期17卷 586-598页

作者： Wan, Guoqing Fan, Zheyu Zhai, Dan-Dan Jiang, Liying Xia, Shengli Gu, Xuefeng Lu, Changlian Shi, Ping Zeng, Xiaobin Meng, Jihong Chen, Nianhong Shanghai Univ Med & Hlth Sci Zhoupu Hosp Shanghai Key Lab Mol Imaging Shanghai 201318 Peoples R China Shanghai Univ Med & Hlth Sci Sch Pharm Shanghai 201318 Peoples R China East China Univ Sci & Technol State Key Lab Bioreactor Engn Shanghai 200237 Peoples R China Henan Univ Technol Coll Biol Engn Zhengzhou 450001 Henan Peoples R China Shenzhen Univ Ctr Lab Longhua Branch Shenzhen 518061 Guangdong Peoples R China Shenzhen Univ Clin Med Coll Jinan Univ 2 Shenzhen Peoples Hosp Dept Infect Dis Shenzhen 518061 Guangdong Peoples R China Shenzhen Univ Guangdong Prov Key Lab Reg Immun & Dis Med Sch Shenzhen 518061 Guangdong Peoples R China Southeast Univ Sch Med Dept Microbiol & Immunol Nanjing 210009 Jiangsu Peoples R China

Objectives Ganoderic acid Me [GA-Me], a major bioactive triterpene extracted from Ganoderma lucidum, is often used to treat immune system diseases caused by viral infections. Although triterpenes have been widely employed in traditional medicine, the comprehensive mechanisms by which GA-Me acts against viral infections have not been reported. Sendai virus [SeV]-infected host cells have been widely employed as an RNA viral model to elucidate the mechanisms of viral infection. Methods In this study, SeV- and mock-infected [Control] cells were treated with or without 54.3 mu M GA-Me. RNA-Seq was performed to identify differentially expressed mRNAs, followed by qRT-PCR validation for selected genes. GO and KEGG analyses were applied to investigate potential mechanisms and critical pathways associated with these genes. Results GA-Me altered the levels of certain genes' mRNA, these genes revealed are associated pathways related to immune processes, including antigen processing and presentation in SeV-infected cells. Multiple signaling pathways, such as the mTOR pathway, chemokine signaling pathway, and the p53 pathways, significantly correlate with GA-Me activity against the SeV infection process. qRT-PCR results were consistent with the trend of RNA-Seq findings. Moreover, PPI network analysis identified 20 crucial target proteins, including MTOR, CDKN2A, MDM2, RPL4, RPS6, CREBBP, UBC, UBB, and NEDD8. GA-Me significantly changed transcriptome-wide mRNA profiles of RNA polymerase II/III, protein posttranslational and immune signaling pathways. Conclusion These results should be further assessed to determine the innate immune response against SeV infection, which might help in elucidating the functions of these genes affected by GA-Me treatment in virus-infected cells, including cells infected with SARS-CoV-2.

关键词： Ganoderic acid Me transcriptomic profiling sendai virus RNA virus SARS-CoV-2 qRT-PCR

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transcriptomic profiling and novel insights into the effect of AG ablation on gonad development in Macrobrachium rosenbergii

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AQUACULTURE 2022年 556卷

作者： Tan, Kianann Yu, Jiongying Liao, Shouli Huang, Jiarui Li, Meng Wang, Weimin Huazhong Agr Univ Coll Fisheries Key Lab Agr Anim Genet Breeding & Reprod Key Lab Freshwater Anim BreedingMinist AgrMinist Wuhan 430070 Peoples R China

Androgenic glands (AGs) regulate male sexual differentiation in M. rosenbergii, and AG ablation may induce sex reversal and male-to-neofemale transformation. However, information on gonad development following AG ablation is scarce. To investigate the effects of gonad development and sex reversal after AG ablation, we utilized transcriptomic profiling, RT-qPCR, and histological and morphological observation. transcriptomic profiling generated 42.32-42.92 million clean reads. A total of 94,747 unigenes were assembled with a total length, average length, N50, and GC content of 160,460,655 bp, 1693 bp, 3438 bp, and 39.86%, respectively. Hsp70, IGFBP7, Mar-Mrr, Serpin, TUBA3, CREB, EF1a, and BMP7 were identified as differentially expressed by gonad transcriptome profiling after AG ablation. Interestingly, the Rap1, Hippo, PI3K, oxytocin, thyroid hormone, and apoptosis signalling pathways were all found to be involved in the sex-reversal process by regulating cell proliferation and gonad development and maintaining homeostasis. Sexual morphology features and histological changes following AG ablation validated the sex reversal from male to neofemale. Sexual manipulation permits monosex culture while considerably improving output yield. Taken together, these findings provide insight into the sexual reversal mechanism of M. rosenbergii after AG ablation. The findings in this study may aid in the future investigation of the sex-reversal mechanisms in other decapod species and offer a new breeding and culture strategy for M. rosenbergii aquaculture industry.

关键词： Macrobrachium rosenbergii Androgenic gland ablation transcriptomic profiling Sex-reversal Gonad development

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The Beneficial Effect of 24-Epibrassinolide Against High-Temperature Stress in Gracilariopsis lemaneiformis Revealed by Physiological Response and transcriptomic profiling

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JOURNAL OF PLANT GROWTH REGULATION 2025年第5期44卷 1948-1962页

作者： Chu, Luke Luo, Suya Chen, Qionglin Chen, Xiaojiao Xu, Nianjun Sun, Xue Ningbo Univ Sch Marine Sci Key Lab Marine Biotechnol Zhejiang Prov Ningbo 315211 Peoples R China

The commercial seaweed Gracilariopsis lemaneiformis is mainly used as raw material for agar production and feed for abalone. The heat-resistant strains G. lemaneiformis are extensively cultivated in the northern and southern coasts of China, yet high temperature in the summertime in southern coasts has hindered the growth and limited the cultivated periods of this seaweed. A vast majority of reports have manifested that exogenous phytohormone brassinosteroids (BRs) can improve the plant heat-tolerance. However, little is known about the effect and its underlying mechanism of BRs in algae. In this study, the effect of 24-epibrassinolide (EBR) on the physiological and transcriptional levels was investigated in the high-temperature stressed G. lemaneiformis. Physiological data indicated that EBR application could improve the growth with 1.43-fold on day 5 and non-photochemical quenching parameter, reduce the productions of reactive oxygen species (ROS) and malondialdehyde (MDA), enhance the accumulations of proline, trehalose, and the levels of endogenous 2-methylthio-N6-isopentenyladenine (2MeSiP), 2-methylthio-cis-zeatin riboside (2MeScZR), jasmonic acid (JA), N-[(-)-jasmonoyl]-(l)-phenylalanine (JA-Phe) and salicylic acid 2-O-beta-glucoside (SAG) under high-temperature condition. In addition, transcriptomic analysis identified 656 upregulated- and 680 downregulated-genes following the EBR treatment compared to the control group, revealed that EBR activated the metabolic pathways of the glycolysis, tricarboxylic acid (TCA) cycle, pentose phosphate pathway, and synthesis of threonine, methionine, and serine. Taken together, the aforementioned results highlighted the beneficial effect of EBR via alleviating the oxidative stress, promoting the accumulations of osmolytes and stress-related phytohormones, and activating the metabolisms of carbohydrate and amino acid, thereby resulting in the mitigating of growth inhibition by high-temperature stress in G. lemaneiformis.

关键词： 24-Epibrassinolide Gracilariopsis lemaneiformis High-temperature stress Physiological response transcriptomic profiling

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How Can Spatial transcriptomic profiling Advance Our Understanding of Skin Diseases?

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JOURNAL OF INVESTIGATIVE DERMATOLOGY 2025年第3期145卷 522-535页

作者： Kumaran, Girishkumar Carroll, Liam Muirhead, Nina Bottomley, Matthew J. Univ Oxford Chinese Acad Med Sci Oxford Inst Nuffield Dept Med Oxford OX1 2JD England Skin Inspect London England

Spatial transcriptomic (ST) profiling is the mapping of gene expression within cell populations with preservation of positional context and represents an exciting new approach to develop our understanding of local and regional influences upon skin biology in health and disease. With the ability to probe from a few hundred transcripts to the entire transcriptome, multiple ST approaches are now widely available. In this paper, we review the ST field and discuss its application to dermatology. Its potential to advance our understanding of skin biology in health and disease is highlighted through the illustrative examples of 3 research areas: cutaneous aging, tumorigenesis, and psoriasis.

关键词： Gene expression mapping Skin tissue transcriptomics Spatial analysis Spatial transcriptomics transcriptomic profiling

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BIOLOGY OF REPRODUCTION 2025年第5期112卷 916-931页

作者： Rogers, Heather M. Gad, Ahmed Cork, Gentry K. Menjivar, Nico G. Schoolcraft, William B. Tesfaye, Dawit Yuan, Ye Colorado Ctr Reprod Med 10290 Ridge Gate Circle Lone Tree CO 80124 USA Colorado State Univ Coll Vet Med & Biomed Sci Dept Biomed Sci Anim Reprod & Biotechnol Lab ARBL Ft Collins CO USA Cairo Univ Fac Agr Dept Anim Prod Giza Egypt

Advanced maternal age (AMA) patients experience decreased success from assisted reproductive technologies (ART), attributed to the quantity and quality of oocytes, which is significantly influenced by the intrafollicular granulosa cells (GCs). In this study, we compared the mRNA and microRNA (miRNA) transcriptomes between young (< 32 years old) and AMA (> 38 years old) patients' GCs to identify potential ovarian aging-related molecular signatures. We identified 293 and 21 differentially expressed genes (DEGs) and miRNAs (DE miRNAs), respectively, between young and aged GCs. Highly expressed mitochondrial-encoded genes, MT-ND3, MT-ND6, and MT-CYB, were downregulated in aged GCs, indicating potential mitochondrial insufficiency. Additionally, pathway analysis indicates DEGs are involved in inflammation, cytokine signaling, extracellular matrix (ECM) remodeling, and angiogenesis. Key DEGs related to these processes include CXCL8, IL1B, NLRP3, SIGIRR, ANGPT2, ADAM8, and ADAMTS14. Additionally, target gene prediction and pathway analysis of DE miRNAs indicates their potential post-transcriptional regulation of genes associated with cell signaling, mitochondrial function, oxidative stress, apoptosis, and senescence pathways in addition to cytokine signaling, angiogenesis, and ECM remodeling. To investigate regulatory mechanisms further, we looked at the DEGs' convergence with the DE miRNAs predicted target genes and we identified miR-483-3p, miR-1268a, miR-4497, miR-7704, miR-135a-5p, miR-1261, and miR-4791 as potential crucial regulators of genes involved in pathways associated with inflammation, ECM, and angiogenesis. This data suggests that aged GCs have an impaired ability to elicit the same pro-inflammatory response combined with dysregulation of angiogenesis and ECM remodeling compared to young GCs, and miRNA may play a role in regulating key ovulatory processes. While this study identifies potential regulatory relationships between DE miRNAs and DEGs, experimental

关键词： ovarian aging granulosa cells ovulation microRNA transcriptomic profiling

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Advanced machine learning framework for enhancing breast cancer diagnostics through transcriptomic profiling

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DISCOVER ONCOLOGY 2025年第1期16卷 1-23页

作者： Saadh, Mohamed J. Ahmed, Hanan Hassan Kareem, Radhwan Abdul Yadav, Anupam Ganesan, Subbulakshmi Shankhyan, Aman Sharma, Girish Chandra Naidu, K. Satyam Rakhmatullaev, Akmal Sameer, Hayder Naji Yaseen, Ahmed Athab, Zainab H. Adil, Mohaned Farhood, Bagher Middle East Univ Fac Pharm Amman 11831 Jordan Alnoor Univ Coll Pharm Mosul Iraq Ahl Al Bayt Univ Kerbala Iraq GLA Univ Dept Comp Engn & Applicat Mathura 281406 India JAIN Sch Sci Dept Chem & Biochem Bangalore Karnataka India Chitkara Univ Inst Engn & Technol Ctr Res Impact & Outcome Rajpura 140401 Punjab India NIMS Univ Rajasthan NIMS Inst Engn & Technol Dept Appl Sci Chem Jaipur India Raghu Engn Coll Dept Chem Visakhapatnam 531162 Andhra Pradesh India Tashkent Pediat Med Inst Dept Fac Pediat Surg Tashkent Uzbekistan Natl Univ Sci & Technol Coll Pharm Dhi Qar 64001 Iraq Gilgamesh Ahliya Univ Baghdad Iraq Al Zahrawi Univ Coll Dept Pharm Karbala Iraq Al Farahidi Univ Pharm Coll Baghdad Iraq Kashan Univ Med Sci Fac Paramed Sci Dept Med Phys & Radiol Kashan *** Iran

PurposeThis study proposes an advanced machine learning (ML) framework for breast cancer diagnostics by integrating transcriptomic profiling with optimized feature selection and classification *** and methodsA dataset of 1759 samples (987 breast cancer patients, 772 healthy controls) was analyzed using Recursive Feature Elimination, Boruta, and ElasticNet for feature selection. Dimensionality reduction techniques, including Non-Negative Matrix Factorization (NMF), Autoencoders, and transformer-based embeddings (BioBERT, DNABERT), were applied to enhance model interpretability. Classifiers such as XGBoost, LightGBM, ensemble voting, Multi-Layer Perceptron, and Stacking were trained using grid search and cross-validation. Model evaluation was conducted using accuracy, AUC, MCC, Kappa Score, ROC, and PR curves, with external validation performed on an independent dataset of 175 *** and LightGBM achieved the highest test accuracies (0.91 and 0.90) and AUC values (up to 0.92), particularly with NMF and BioBERT. The ensemble Voting method exhibited the best external accuracy (0.92), confirming its robustness. Transformer-based embeddings and advanced feature selection techniques significantly improved model performance compared to conventional approaches like PCA and Decision *** proposed ML framework enhances diagnostic accuracy and interpretability, demonstrating strong generalizability on an external dataset. These findings highlight its potential for precision oncology and personalized breast cancer diagnostics.

关键词： Breast cancer Machine learning transcriptomic profiling Feature selection Predictive modeling Biomarkers

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CTPAD: an interactive web application for comprehensive transcriptomic profiling in allergic diseases

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JOURNAL OF TRANSLATIONAL MEDICINE 2024年第1期22卷 935页

作者： Zhou, Suizi Huang, Wanqiao Liu, Yitong Luo, Peng Lin, Anqi Yang, Hong Qiu, Qianhui Guangdong Acad Med Sci Guangdong Prov Peoples Hosp Guangdong Cardiovasc Inst Guangzhou Peoples R China Southern Med Univ Guangdong Prov Peoples Hosp Guangdong Acad Med Sci Dept Otolaryngol Head & Neck Surg Guangzhou 510000 Guangdong Peoples R China Southern Med Univ Zhujiang Hosp Dept Oncol Guangzhou Peoples R China

BackgroundAllergic diseases are systemic chronic inflammatory diseases associated with multiorgan damage and complex pathogenesis. Several studies have revealed the association of gene expression abnormalities with the development of allergic diseases, but the biomedical field still lacks a public platform for comprehensive analysis and visualization of transcriptomic data of allergic *** aim of the study is to provide a comprehensive web tool for multiple analysis in allergic *** retrieved and downloaded human and mouse gene expression profile data associated with allergic diseases from the Gene Expression Omnibus (GEO) database and standardized the data uniformly. We used gene sets obtained from the MSigDB database for pathway enrichment analysis and multiple immune infiltration algorithms for the estimation of immune cell proportion. The basic construction of the web pages was based on the Shiny framework. Additionally, more convenient features were added to the server to improve the efficiency of the web pages, such as jQuery plugins and a comment box to collect user *** developed CTPAD, an interactive R Shiny application that integrates public databases and multiple algorithms to explore allergic disease-related datasets and implement rich transcriptomic visualization capabilities, including gene expression analysis, pathway enrichment analysis, immune infiltration analysis, correlation analysis, and single-cell RNA sequencing analysis. All functional modules offer customization options and can be downloaded in PDF format with high-resolution *** largely facilitates the work of researchers without bioinformatics background to enable them to better explore the transcriptomic features associated with allergic diseases. CTPAD is available at https://***/CTPAD/.

关键词： Allergic diseases transcriptomic profiling Visualization Gene Bioinformatics

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transcriptomic profiling and regulatory pathways of cardiac resident macrophages in aging

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CELLULAR AND MOLECULAR LIFE SCIENCES 2024年第1期81卷 220-220页

作者： Xia, Guofang Zhu, Simeng Liu, Yujia Pan, Jingwei Wang, Xiaoqing Shen, Chengxing Du, Ailian Xu, Congfeng Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6 Dept Cardiol Sch Med Shanghai Peoples R China Shanghai Jiao Tong Univ Sch Med Tongren Hosp Dept Neurol Shanghai Peoples R China Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp S Dept Cardiol Chengdu Peoples R China

Cardiovascular diseases are an array of age-related disorders, and accumulating evidence suggests a link between cardiac resident macrophages (CRMs) and the age-related disorders. However, how does CRMs alter with aging remains elusive. In the present study, aged mice (20 months old) have been employed to check for their cardiac structural and functional alterations, and the changes in the proportion of CRM subsets as well, followed by sorting of CRMs, including C-C Motif Chemokine Receptor 2 (CCR2)+ and CCR2- CRMs, which were subjected to Smart-Seq. Integrated analysis of the Smart-Seq data with three publicly available single-cell RNA-seq datasets revealed that inflammatory genes were drastic upregulated for both CCR2+ and CCR2- CRMs with aging, but genes germane to wound healing were downregulated for CCR2- CRMs, suggesting the differential functions of these two subsets. More importantly, inflammatory genes involved in damage sensing, complement cascades, and phagocytosis were largely upregulated in CCR2- CRMs, implying the imbalance of inflammatory response upon aging. Our work provides a comprehensive framework and transcriptional resource for assessing the impact of aging on CRMs with a potential for further understanding cardiac aging.

关键词： Aging Macrophages Cardiac resident macrophages transcriptomic profiling Smart-Seq

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