Article
Biochemistry & Molecular Biology
Tosin Opadokun, Jeffrey Agyapong, Petra Rohrbach
Summary: This study preliminarily characterized the EVs released from RBCs infected with different stages of malaria parasites and found that they exhibit distinct protein expression profiles.
Article
Endocrinology & Metabolism
Yao Xie, Yongli Ji, Yunrui Lu, Yuankun Ma, Hui Ni, Jian Shen, Hong Ma, Chunna Jin, Yuwen Chen, Yan Lin, Meixiang Xiang
Summary: This study used single-cell analysis to compare the heterogeneity, functions, and cell fates of subcutaneous adipose-derived stem cells (SUB-ADSCs) and perivascular ADSCs (PV-ADSCs). Four subpopulations of PV-ADSCs were identified, with the Clec11a+ subpopulation potentially regulating the differentiation of PV-ADSCs towards a smooth muscle cell phenotype. The study revealed distinct characteristics between PV-ADSCs and SUB-ADSCs.
Article
Biochemistry & Molecular Biology
Juneyoung Lee, Attayeb Mohsen, Anik Banerjee, Louise D. McCullough, Kenji Mizuguchi, Motomu Shimaoka, Hiroshi Kiyono, Eun Jeong Park
Summary: The intestinal epithelium serves as a dynamic barrier that senses inflammatory signals in the gut environment, modulating phenotypic changes in response. With aging, dysregulation of miRNAs in intestinal epithelial cells is observed, leading to compromised barrier function and increased inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Natalia Atzemian, Dimitra Kareli, Georgia Ragia, Vangelis G. Manolopoulos
Summary: Direct Oral Anticoagulants (DOACs) not only have anticoagulant effects, but also exhibit pleiotropic actions such as anti-inflammatory and anti-oxidant effects, contributing to cardiovascular protection. This review provides an overview of the effects of DOACs on endothelial cells (ECs) and their underlying mechanisms, highlighting potential differences among DOACs. Further research is needed to fully understand the pleiotropic effects of DOACs on ECs and their mechanisms, as well as the heterogeneity between different DOACs.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Olga Bondareva, Jesus Rafael Rodriguez-Aguilera, Fabiana Oliveira, Longsheng Liao, Alina Rose, Anubhuti Gupta, Kunal Singh, Florian Geier, Jenny Schuster, Jes-Niels Boeckel, Joerg M. Buescher, Shrey Kohli, Nora Kloeting, Berend Isermann, Matthias Blueher, Bilal N. Sheikh
Summary: Obesity has organ- and endothelial cell subtype-specific effects on gene expression networks, including lipid handling, metabolic pathways, and inflammatory signaling. These transcriptomic aberrations worsen with sustained obesity and are only partially mitigated by dietary intervention and weight loss. The study provides insights into the impact of obesity on the endothelium and identifies potential therapeutic targets.
Review
Cell Biology
Wen-Ting Chen, Yi Luo, Xue-Mei Chen, Jian-Hui Xiao
Summary: Chronic wounds in diabetes patients can lead to severe disabilities, and impaired angiogenesis hinders wound healing. Stem cells, with their powerful paracrine properties, offer a potential solution by alleviating the pathogenesis of chronic diabetic wounds and even curing them. Exosome-derived miRNAs, important components of stem cell paracrine signaling, have shown promise in regulating vascular function and promoting the repair and regeneration of skin wounds.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Martina Rudnicki, Alexandra Pislaru, Omid Rezvan, Eric Rullman, Aly Fawzy, Emmanuel Nwadozi, Emilie Roudier, Thomas Gustafsson, Tara L. Haas
Summary: Female mice exhibit greater adipose angiogenesis and healthier adipose tissue compared to males when fed a high-fat diet. Transcriptome analysis reveals that female adipose endothelial cells (EC) have upregulated genes related to proliferation, oxidative phosphorylation, and chromatin remodeling, while male EC genes are enriched for inflammation and senescence-associated secretory. These sex-biased phenotypes of adipose EC are also observed in aged EC. Our findings provide insights into the molecular mechanisms that differentiate male and female EC responses to pathophysiological conditions.
Article
Biochemistry & Molecular Biology
Peter C. Chan-Andersen, Elena Romanova, Stanislav S. Rubakhin, Jonathan Sweedler
Summary: This study used microscopy-guided, high-throughput mass spectrometry to investigate the neuropeptide heterogeneity in the California sea hare. They identified 40 unique neuronal populations with distinct neuropeptide profiles, some of which were behaviorally related. This mass spectrometry-based approach offers a robust categorization of large cell populations based on single cell neuropeptide content and can be applied to various animals and tissues.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Xizhao Chen, Mansheng Li, Songbiao Zhu, Yang Lu, Shuwei Duan, Xu Wang, Yong Wang, Pu Chen, Jie Wu, Di Wu, Zhe Feng, Guangyan Cai, Yunping Zhu, Haiteng Deng, Xiangmei Chen
Summary: We constructed a quantitative proteome atlas for IgA nephropathy (IgAN) and identified three subtypes based on proteomic profiles. We found differences in protein expression, subcellular injury, and extracellular accumulation among the subtypes. The complement mitochondrial extracellular (CME) pathway showed high diagnostic potential in distinguishing IgAN subtypes. Moreover, proteins related to glial cells, endothelial cells, and tubular interstitial fibrosis were highly expressed in certain subtypes and associated with worse prognosis.
Article
Oncology
Ashok Narasimhan, Xiaoling Zhong, Ernie P. Au, Eugene P. Ceppa, Atilla Nakeeb, Michael G. House, Nicholas J. Zyromski, C. Max Schmidt, Katheryn N. H. Schloss, Daniel E. I. Schloss, Yunlong Liu, Guanglong Jiang, Bradley A. Hancock, Milan Radovich, Joshua K. Kays, Safi Shahda, Marion E. Couch, Leonidas G. Koniaris, Teresa A. Zimmers
Summary: The majority of PDAC patients suffer from cachexia, but our study suggests that adipose tissue loss may play a more important role in PDAC cachexia. We aim to understand the concurrent muscle and adipose changes in cachexia and have identified independently targetable mechanisms for muscle and adipose wasting.
Article
Medicine, Research & Experimental
Garrett S. Dunlap, Allison C. Billi, Xianying Xing, Feiyang Ma, Mitra P. Maz, Lam C. Tsoi, Rachael Wasikowski, Jeffrey B. Hodgin, Johann E. Gudjonsson, J. Michelle Kahlenberg, Deepak A. Rao
Summary: This study provides a detailed single-cell RNA-Seq profile of T and NK cells in cutaneous lupus, revealing elevated expression of IFN-stimulated genes in T cells from lesional skin biopsies. While skin T cells from cutaneous lupus lesions did not show increased activation, cytotoxicity, or exhaustion compared to control skin, they did exhibit an elevated ISG signature compared to systemic sclerosis skin biopsies.
Article
Immunology
Simone Brioschi, Julia A. Belk, Vincent Peng, Martina Molgora, Patrick Fernandes Rodrigues, Khai M. Nguyen, Shoutang Wang, Siling Du, Wei -Le Wang, Gary E. Grajales-Reyes, Jennifer M. Ponce, Carla M. Yuede, Qingyun Li, John M. Baer, David G. DeNardo, Susan Gilfillan, Marina Cella, Ansuman T. Satpathy, Marco Colonna
Summary: A constitutive Cre line controlled by Crybb1 gene was generated to target microglia in embryonic brain macrophages. This tool allowed for the differentiation of embryonic-derived and monocyte-derived BAMs in the mouse cortex. By deleting the transcription factor SMAD4, microglia and embryonic-derived BAMs acquired a BAM specification signature. Meanwhile, genuine BAMs remained unaffected. The study sheds light on the role of SMAD4 in microglia commitment and highlights the importance of Crybb1-Cre as a tool for targeting embryonic brain macrophages.
Article
Cell Biology
Chris Still II, Wen-Teh Chang, Seth L. Sherman, Kyle R. Sochacki, Jason L. Dragoo, Lei S. Qi
Summary: Single cell transcriptomic profiling of tendon progenitor cells reveals seven distinct subpopulations, including those responsive to mechanical stress, highly clonogenic, and specialized in cytokine or growth factor expression, laying the foundation for further investigation into the pathology and molecular hallmarks of tendinopathy under mechanical stimulation conditions.
CELL REPORTS MEDICINE
(2021)
Article
Immunology
Cheng Feng, Mengjie Shan, Yijun Xia, Zhi Zheng, Kai He, Yingxin Wei, Kexin Song, Tian Meng, Hao Liu, Yan Hao, Zhengyun Liang, Youbin Wang, Yongsheng Huang
Summary: In this study, the cellular composition of keloids was analyzed using single-cell RNA sequencing. Significant differences were found in most cell types between keloid and adjacent normal tissue. The study also revealed distinctive immune profiles in keloids, including an increased proportion of macrophages and decreased proportion of cDC2 cells. Additionally, tumor-associated macrophage characteristics were upregulated in advanced keloid cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Hyon-Xhi Tan, Jennifer A. Juno, Robyn Esterbauer, Hannah G. Kelly, Kathleen M. Wragg, Penny Konstandopoulos, Sheilajen Alcantara, Carolina Alvarado, Robert Jones, Graham Starkey, Boa Zhong Wang, Osamu Yoshino, Thomas Tiang, M. Lindsay Grayson, Helen Opdam, Rohit D'Costa, Angela Vago, Laura K. Mackay, Claire L. Gordon, David Masopust, Joanna R. Groom, Stephen J. Kent, Adam K. Wheatley
Summary: Recent studies have found that memory B cells can reside in inflamed tissues for a long time. This study characterized tissue-resident memory B cells in the lungs of mice after influenza infection and discovered that the mechanisms underlying their localization may be evolutionarily conserved.
SCIENCE IMMUNOLOGY
(2022)
Article
Neurosciences
Minna Oksanen, Ida Hyotylainen, Kalevi Trontti, Taisia Rolova, Sara Wojciechowski, Marja Koskuvi, Matti Viitanen, Anna-Liisa Levonen, Iiris Hovatta, Laurent Roybon, Sarka Lehtonen, Katja M. Kanninen, Riikka H. Hamalainen, Jari Koistinaho
Article
Biochemistry & Molecular Biology
Uma Thanigai Arasu, Ashik Jawahar Deen, Sanna Pasonen-Seppanen, Sami Heikkinen, Maciej Lalowski, Riikka Karna, Kai Harkonen, Petri Makinen, Elisa Lazaro-Ibanez, Pia R-M Siljander, Sanna Oikari, Anna-Liisa Levonen, Kirsi Rilla
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Jenni Kublbeck, Taina Vuorio, Jonna Niskanen, Vittorio Fortino, Albert Braeuning, Khaled Abass, Arja Rautio, Jukka Hakkola, Paavo Honkakoski, Anna-Liisa Levonen
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cardiac & Cardiovascular Systems
Suvi Linna-Kuosmanen, Vanesa Tomas Bosch, Pierre R. Moreau, Maria Bouvy-Liivrand, Henri Niskanen, Emilia Kansanen, Annukka Kivela, Juha Hartikainen, Mikko Hippelainen, Hannu Kokki, Pasi Tavi, Anna-Liisa Levonen, Minna U. Kaikkonen
Summary: This study investigated the genome-wide effects of oxidized phospholipids on transcriptional gene regulation in endothelial cells, focusing on the role of miRNAs and NRF2 transcription factor. The results showed that NRF2 plays a key role in up-regulated transcripts and transcriptional initiation in response to oxidized phospholipids. Furthermore, NRF2 was identified as a novel regulator of over 100 endothelial pri-miRNAs, with miR-21-5p and miR-100-5p demonstrating opposing roles in gene expressions and potential correlation with the severity of coronary artery disease.
CARDIOVASCULAR RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Lidia Cedo, Jari Metso, David Santos, Annabel Garcia-Leon, Nuria Plana, Sonia Sabate-Soler, Noemi Rotllan, Andrea Rivas-Urbina, Karen A. Mendez-Lara, Mireia Tondo, Josefa Girona, Josep Julve, Victor Pallares, Aleyda Benitez-Amaro, Vicenta Llorente-Cortes, Antonio Perez, Diego Gomez-Coronado, Anna-Kaisa Ruotsalainen, Anna-Liisa Levonen, Jose Luis Sanchez-Quesada, Luis Masana, Petri T. Kovanen, Matti Jauhiainen, Miriam Lee-Rueckert, Francisco Blanco-Vaca, Joan Carles Escola-Gil
CIRCULATION RESEARCH
(2020)
Article
Genetics & Heredity
Ilakya Selvarajan, Anu Toropainen, Kristina M. Garske, Maykel Lopez Rodriguez, Arthur Ko, Zong Miao, Dorota Kaminska, Kadri Ounap, Tiit Ord, Aarthi Ravindran, Oscar H. Liu, Pierre R. Moreau, Ashik Jawahar Deen, Ville Mannisto, Calvin Pan, Anna-Liisa Levonen, Aldons J. Lusis, Sami Heikkinen, Casey E. Romanoski, Jussi Pihlajamaki, Paivi Pajukanta, Minna U. Kaikkonen
Summary: Genetic factors underlying coronary artery disease (CAD) have been extensively studied using genome-wide association studies (GWAS). This study identified potential target genes related to liver function by analyzing the function of non-coding single-nucleotide polymorphisms in CAD GWAS loci located within liver-specific enhancer elements. Furthermore, the analysis identified a significant number of unique SNPs with allele-specific regulatory activity, particularly enhancers near key genes involved in cholesterol homeostasis.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Hematology
Pierre R. Moreau, Vanesa Tomas Bosch, Maria Bouvy-Liivrand, Kadri Ounap, Tiit Ord, Heidi H. Pulkkinen, Petri Polonen, Merja Heinaniemi, Seppo Yla-Herttuala, Johanna P. Laakkonen, Suvi Linna-Kuosmanen, Minna U. Kaikkonen
Summary: This study aimed to characterize microRNA-related regulatory mechanisms in the aorta during atherosclerosis. The research analyzed miRNA expression changes in different cell types under proatherogenic stimuli and found common miRNA species dominating in all cell types. The study identified potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Environmental Sciences
A. Sakhteman, M. Failli, J. Kublbeck, A. L. Levonen, V. Fortino
Summary: The study developed predictive models based on gene expression data to efficiently identify and prioritize EDCs, revealing key metabolic pathways and genes affected by EDCs.
ENVIRONMENT INTERNATIONAL
(2021)
Article
Oncology
Miika Mehine, Terhi Ahvenainen, Sara Khamaiseh, Jouni Harkonen, Siiri Reinikka, Tuomas Heikkinen, Anna Ayravainen, Paivi Pakarinen, Paivi Harkki, Annukka Pasanen, Anna-Liisa Levonen, Ralf Butzow, Pia Vahteristo
Summary: A novel subtype of uterine leiomyomas has been identified, characterized by distinct molecular features, mutations disrupting neddylation of the Cullin 3-RING E3 ligase, and activation of the NRF2 pathway. These findings provide new opportunities for targeted treatment of uterine leiomyomas.
Article
Oncology
Sarang S. Talwelkar, Mikko I. Mayranpaa, Julia Schuler, Nora Linnavirta, Annabrita Hemmes, Simone Adinolfi, Matti Kankainen, Wolfgang Sommergruber, Anna-Liisa Levonen, Jari Rasanen, Aija Knuuttila, Emmy W. Verschuren, Krister Wennerberg
Summary: Treatment with ALK inhibitors improves outcome for NSCLC patients with ALK-rearranged tumors, but resistance typically develops. In this study, tumor cell cultures were generated from an ALK-rearranged tumor specimen and drug screens identified a role for PI3K beta and EGFR inhibition in enhancing ALK-inhibitor response and preventing resistance. Combinatorial treatment with ALK and PI3K beta inhibitors showed promise in targeting ALK-rearranged NSCLC.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jouni Harkonen, Petri Polonen, Ashik Jawahar Deen, Ilakya Selvarajan, Hanna-Riikka Teppo, Elitsa Y. Dimova, Thomas Kietzmann, Maarit Ahtiainen, Juha P. Vayrynen, Sara A. Vayrynen, Hanna Elomaa, Niko Tynkkynen, Tiia Eklund, Teijo Kuopio, Eva-Maria Talvitie, Pekka Taimen, Markku Kallajoki, Minna U. Kaikkonen, Merja Heinaniemi, Anna-Liisa Levonen
Summary: The NRF2 pathway is frequently activated in various cancer types, but a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and conducted a pan-cancer analysis of oncogenic NRF2 signaling using it. Our findings revealed an immunoevasive phenotype in squamous malignancies of the lung, head and neck area, cervix, and esophagus, where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression, and T cell and macrophage infiltration. These tumors have a molecular phenotype with amplification of SOX2/TP63, TP53 mutation, and CDKN2A loss, and are associated with upregulation of immunomodulatory genes NAMPT, WNT5A, SPP1, SLC7A11, SLC2A1, and PD-L1. Our functional genomics analyses suggest that these genes are candidate NRF2 targets, indicating a direct modulation of the tumor immune milieu. Single-cell mRNA data shows that cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands and increased expression of immunosuppressive ligands NAMPT, SPP1, and WNT5A involved in intercellular crosstalk. Moreover, the negative relationship between NRF2 and immune cells is explained by stromal populations of lung squamous cell carcinoma, indicating a potential effect across multiple squamous malignancies based on our molecular subtyping and deconvolution data.
Article
Biochemistry & Molecular Biology
Simone Adinolfi, Tommi Patinen, Ashik Jawahar Deen, Sini Pitkänen, Jouni Härkönen, Emilia Kansanen, Jenni Küblbeck, Anna-Liisa Levonen
Summary: The KEAP1-NRF2 pathway is a crucial regulator of cellular defense against oxidative and electrophilic stimuli, playing a significant role in various disease pathologies. Research focused on understanding NRF2 signaling and its downstream effects has led to the identification of novel therapeutic targets. This graphical review provides an updated overview of the KEAP1-NRF2 signaling, highlighting recent advancements in the field, including the mechanism of NRF2 activation and its potential application in cancer diagnostics and treatment.
