Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections by J Alfred Witjes, Alina Vrieling, Mihai G Netea, Leo A B Joosten, Katja K H Aben, Sita H Vermeulen, Joost L Boormans, Antoine G van der Heijden, Boris Novakovic, Jelmer H van Puffelen, Liesbeth van Emst, Denise Kooper, Tahlita C M Zuiverloon, Ursula T H Oldenhof, Tessel E Galesloot, Lambertus A L M Kiemeney, Egbert Oosterwijk

“…An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. …”
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Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism by Rocio Diaz Escarcega, Vijay Kumar M. J., Vasilia E. Kyriakopoulos, Guadalupe J. Ortiz, Aaron M. Gusdon, Huihui Fan, Pedram Peesh, Maria P. Blasco Conesa, Gabriela Delevati Colpo, Hilda W. Ahnstedt, Lucy Couture, Stella H. Kim, Miriam Hinojosa, Christine M. Farrell, Sean P. Marrelli, Akihiko Urayama, Bhanu P. Ganesh, Paul E. Schulz, Louise D. McCullough, Andrey S. Tsvetkov

“…In cultured astrocytes, 1-arachidonoyl glycerol promoted phosphorylation of the transcriptional regulator sphingosine kinase 2, which was inhibited by the transient receptor potential vanilloid 1 receptor antagonists, as well as chromatin remodelling. Overall, we identified novel sex-specific metabolites in MCI patients that could serve as biomarkers of MCI in both sexes, help further define AD etiology, and reveal new potential prevention strategies for AD.…”
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MSC-exosomes pretreated by Danshensu extracts pretreating to target the hsa-miR-27a-5p and STAT3-SHANK2 to enhanced antifibrotic therapy by Jiabin Liang, Jingxiu Zhao, Lin Yang, Qian Wang, Jing Liao, Jianhao Li, Weizhao Zhuang, Fanghong Li, Jinxian He, Yukuan Tang, Hanwei Chen, Chen Huang

“…Mechanistic insights were gained through the analysis of the STAT3/HIF-1α/VEGF signaling pathway, tissue dual-fluorescence localization,chromatin immunoprecipitation sequencing (ChIP-seq), and dual-luciferase reporter (DLR) assays. …”
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Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy by Coraline Radermecker, Pascale Hubert, Patrick Roncarati, Stephanie Demoulin, Charlotte Pilard, Marie Ancion, Celia Reynders, Thomas Lerho, Diane Bruyere, Alizee Lebeau, Margot Meunier, Marie-Julie Nokin, Elodie Hendrick, Olivier Peulen, Philippe Delvenne, Michael Herfs

“…Background High-mobility group box 1 (HMGB1) is a multifunctional redox-sensitive protein involved in various intracellular (eg, chromatin remodeling, transcription, autophagy) and extracellular (inflammation, autoimmunity) processes. …”
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Uncovering Molecular Mechanisms of Feed Efficiency in Pigs Through Multi-Omics Analysis of the Jejunum by Saixian Zhang, Yue Xiang, Yaobang Jian, Qiulin Zhao, Jiahui Sun, Yi Huang, Jing Xu, Xiaolong Qi, Jingjin Li, Zhuqing Zheng, Liangliang Fu, Yuwen Liu, Xinyun Li

“…By comparing gene expression and chromatin accessibility profiles in the jejunum, we identified key differentially expressed genes (DEGs) and differentially accessible regions (DARs) associated with lipid metabolism and immune function, both of which are critical pathways for efficient growth. …”
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Metformin exerted tumoricidal effects on colon cancer tumoroids via the regulation of autophagy pathway by Roya Shabkhizan, Çığır Biray Avci, Sanya Haiaty, Marziyeh Sadat Moslehian, Fatemeh Sadeghsoltani, Ahad Bazmani, Mahdi Mahdipour, Leila Sabour Takanlou, Maryam Sabour Takanlou, Arezoo Rezaie Nezhad Zamani, Reza Rahbarghazi

“…Histological examination confirmed the loosening integrity of tumoroids in MTF-treated groups, especially 120 mM MTF, with the increase in cell death via the induction of apoptosis (chromatin marginalization) and necrotic (pyknotic nuclei) changes. …”
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Mina53 catalyzes arginine demethylation of p53 to promote tumor growth by Lixiao Zhou, Liyang Yu, Shushu Song, Yong Wang, Qiang Zhu, Meng Li, Yutong Sha, Liang Xu, Xin Shu, Qingqing Liao, Ting Wu, Bing Yang, Siyuan Chai, Bingyi Lin, Liming Wu, Ruhong Zhou, Xiaotao Duan, Chenggang Zhu, Yuanyuan Ruan, Wen Yi

“…Mina53-mediated demethylation reduces p53 stability and oligomerization and alters chromatin modifications at the gene promoter, thereby suppressing p53-mediated transcriptional activation and cell-cycle arrest. …”
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IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells by Laetitia Camard, Tharshana Stephen, Hanane Yahia-Cherbal, Vincent Guillemot, Sébastien Mella, Victoire Baillet, Hélène Lopez-Maestre, Daniele Capocefalo, Laura Cantini, Claire Leloup, Julie Marsande, Katherine Garro, Juan Sienes Bailo, Ambre Dangien, Natalia Pietrosemoli, Milena Hasan, Huimeng Wang, Sidonia B.G. Eckle, Anne M. Fourie, Carrie Greving, Barbara Joyce-Shaikh, Raphaelle Parker, Daniel J. Cua, Elisabetta Bianchi, Lars Rogge

“…Integrated analysis of transcriptomes and chromatin accessibility, supported by CRISPR-Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. …”
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Defining ortholog-specific UHRF1 inhibition by STELLA for cancer therapy by Wenjing Bai, Jinxin Xu, Wenbin Gu, Danyang Wang, Ying Cui, Weidong Rong, Xiaoan Du, Xiaoxia Li, Cuicui Xia, Qingqing Gan, Guantao He, Huahui Guo, Jinfeng Deng, Yuqiong Wu, Ray-Whay Chiu Yen, Srinivasan Yegnasubramanian, Scott B. Rothbart, Cheng Luo, Linping Wu, Jinsong Liu, Stephen B. Baylin, Xiangqian Kong

“…Abstract UHRF1 maintains DNA methylation by recruiting DNA methyltransferases to chromatin. In mouse, these dynamics are potently antagonized by a natural UHRF1 inhibitory protein STELLA, while the comparable effects of its human ortholog are insufficiently characterized, especially in cancer cells. …”
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An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants by Bruce Nmezi, Guillermo Rodriguez Bey, Talia DeFrancesco Oranburg, Kseniia Dudnyk, Santana M. Lardo, Nathan Herdman, Anastasia Jacko, Sandy Rubio, Emanuel Loeza-Alcocer, Julia Kofler, Dongkyeong Kim, Julia Rankin, Emma Kivuva, Nicholas Gutowski, Katherine Schon, Jelle van den Ameele, Patrick F. Chinnery, Sérgio B. Sousa, Filipe Palavra, Camilo Toro, Filippo Pinto e Vairo, Jonas Saute, Lisa Pan, Murad Alturkustani, Robert Hammond, Francois Gros-Louis, Michael S. Gold, Yungki Park, Geneviève Bernard, Raili Raininko, Jian Zhou, Sarah J. Hainer, Quasar S. Padiath

“…This element consists of CTCF binding sites that mediate three-dimensional chromatin looping involving LMNB1 and the recruitment of the PRC2 transcriptional repressor complex. …”
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An exceptionally rare case of a diffuse midline glioma with concomitant H3.1 K27M and G34R mutations in the HIST1H3C (H3C3) gene by Zita Reisz, Rita Pereira, Smitha Nevis, Alan Mackay, Leena Bhaw, Yura Grabovska, Ross Laxton, Valeria Molinari, Anna Burford, Barnaby Clark, Cristina Bleil, Bassel Zebian, Erika Pace, Annette Weiser, Fernando Carceller, Lynley Marshall, Andrew King, Istvan Bodi, Safa Al-Sarraj, Chris Jones, Matthew Clarke

“…A patient-derived cell culture was established enabling unbiased in vitro drug screening; no selective sensitivities were identified. Chromatin immunoprecipitation assays with sequencing (ChIP-seq; H3K27ac, H3K27me3, H3K36me3, RNApol2 marks) showed features in keeping with DMG H3 K27M-mutant tumours (H3K27ac loci including OLIG2, IRX1/2, PKDCC). …”
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Molecular Characterization of the Tumor Suppressor Candidate 5 Gene: Regulation by PPARγ and Identification of TUSC5 Coding Variants in Lean and Obese Humans by Trina A. Knotts, Hyun Woo Lee, Jae Bum Kim, Pieter J. Oort, Ruth McPherson, Robert Dent, Keisuke Tachibana, Takefumi Doi, Songtao Yu, Janardan K. Reddy, Kenji Uno, Hideki Katagiri, Magdalena Pasarica, Steven R. Smith, Dorothy D. Sears, Michel Grino, Sean H. Adams

“…Induction of Tusc5 mRNA levels in 3T3-L1 adipocytes by troglitazone and GW1929 followed a dose-response consistent with these agents' binding affinities for PPARγ. Chromatin immunoprecipitation (ChIP) experiments confirmed that PPARγ protein binds a ∼−1.1 kb promotor sequence of murine TUSC5 transiently during 3T3-L1 adipogenesis, concurrent with histone H3 acetylation. …”
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Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immun... by Qian Yang, Ruijing Zhang, Peng Tang, Yu Sun, Candice Johnson, Jason Saredy, Susu Wu, Jiwei Wang, Yifan Lu, Fatma Saaoud, Ying Shao, Charles Drummer, Keman Xu, Daohai Yu, Rongshan Li, Shuping Ge, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

“…We made the following findings: (1) LIUS upregulates proinflammatory IGs and downregulates metastasis genes in cancer cells, and LIUS upregulates adaptive immunity pathways but inhibits danger-sensing and inflammation pathways and promote tolerogenic differentiation in bone marrow (BM) cells. (2) LIUS upregulates IGs encoded for proteins localized in the cytoplasm, extracellular space, and others, but downregulates IG proteins localized in nuclear and plasma membranes, and LIUS downregulates phosphatases. (3) LIUS-modulated IGs act partially via several important pathways of reactive oxygen species (ROS), reverse signaling of immune checkpoint receptors B7-H4 and BTNL2, inflammatory cytokines, and static or oscillatory shear stress and heat generation, among which ROS is a dominant mechanism. (4) LIUS upregulates trained immunity enzymes in lymphoma cells and downregulates trained immunity enzymes and presumably establishes trained tolerance in BM cells. (5) LIUS modulates chromatin long-range interactions to differentially regulate IGs expression in cancer cells and noncancer cells. …”
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EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis by regulating endoplasmic reticulum stress in knee osteoarthritis by Yang Chen, Shanshan Dong, Xin Zeng, Qing Xu, Mingwei Liang, Guangneng Liao, Lan Li, Bin Shen, Yanrong Lu, Haibo Si, Peifang Wei

“…The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. …”
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Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility by Rosalyn W Sayaman, Masaru Miyano, Eric G Carlson, Parijat Senapati, Arrianna Zirbes, Sundus F Shalabi, Michael E Todhunter, Victoria E Seewaldt, Susan L Neuhausen, Martha R Stampfer, Dustin E Schones, Mark A LaBarge

“…Age-dependent variant responses were common to both lineages, whereas directional changes were almost exclusively detected in luminal epithelia and involved altered regulation of chromatin and genome organizers such as SATB1. Epithelial expression variance of gap junction protein GJB6 increased with age, and modulation of GJB6 expression in heterochronous co-cultures revealed that it provided a communication conduit from myoepithelial cells that drove directional change in luminal cells. …”
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GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma by Meng Li, Yuan Gao, Wei Zhang, Zhijun Tan, Kuo Zhang, Zhaowei Wang, Lei He, Weina Li, Chuanyang Xu, Jieyu Zhang, Desheng Wang, Kefeng Dou, Ran Zhuang, Boquan Jin, Qiang Hao, Wangqian Zhang, Shuning Wang, Jintao Gu, Lei Shang, Haichuan Su, Yingqi Zhang, Cun Zhang

“…We used flow cytometry, coimmunoprecipitation, RNA sequencing, mass spectrum, chromatin immunoprecipitation and Gdf15–/–, OT-I and GFP transgenic mice to demonstrate the effects of GDF15 on Treg cells and related molecular mechanism. …”
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Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma by Soniya Bastola, Marat S. Pavlyukov, Neel Sharma, Yasmin Ghochani, Mayu A. Nakano, Sree Deepthi Muthukrishnan, Sang Yul Yu, Min Soo Kim, Alireza Sohrabi, Natalia P. Biscola, Daisuke Yamashita, Ksenia S. Anufrieva, Tatyana F. Kovalenko, Grace Jung, Tomas Ganz, Beatrice O’Brien, Riki Kawaguchi, Yue Qin, Stephanie K. Seidlits, Alma L. Burlingame, Juan A. Oses-Prieto, Leif A. Havton, Steven A. Goldman, Anita B. Hjelmeland, Ichiro Nakano, Harley I. Kornblum

“…Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing stable phenotypic changes in GBM cells. …”
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HINT1 suppression protects against age-related cardiac dysfunction by enhancing mitochondrial biogenesis by Michio Sato, Tsuyoshi Kadomatsu, Jun Morinaga, Yuya Kinoshita, Daisuke Torigoe, Haruki Horiguchi, Sumio Ohtsuki, Shuji Yamamura, Ryoko Kusaba, Takanori Yamaguchi, Goro Yoshioka, Kimi Araki, Tomohiko Wakayama, Keishi Miyata, Koichi Node, Yuichi Oike

“…We also showed that activity of the BAF chromatin remodeling complex is repressed by HINT1, whose expression in heart increases with age, leading to decreased transcription of Tfam, which promotes mitochondrial biogenesis. …”
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Single-cell multiomics reveal divergent effects of DNMT3A- and TET2-mutant clonal hematopoiesis in inflammatory response by Wazim Mohammed Ismail, Jenna A. Fernandez, Moritz Binder, Terra L. Lasho, Minsuk Kim, Susan M. Geyer, Amelia Mazzone, Christy M. Finke, Abhishek A. Mangaonkar, Jeong-Heon Lee, Liguo Wang, Kwan Hyun Kim, Vernadette A. Simon, Fariborz Rakhshan Rohakthar, Amik Munankarmy, Seul Kee Byeon, Susan M. Schwager, Jonathan J. Harrington, Melissa R. Snyder, Keith D. Robertson, Akhilesh Pandey, Eric D. Wieben, Nicholas Chia, Alexandre Gaspar-Maia, Mrinal M. Patnaik

“…Finally, we show with single-cell resolution that the loss of function of DNMT3A is directly associated with increased chromatin accessibility in mutant cells. Hence, we demonstrate the negative prognostic impact of DNMT3Amt CH on COVID-19–related ARDS and mortality. …”
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Epithelial NSD2 maintains FMO‐mediated taurine biosynthesis to prevent intestinal barrier disruption by Yue Xu, Xiuying Xiao, Chunxiao Ma, Ziyi Wang, Wenxin Feng, Hanyu Rao, Wei Zhang, Ningyuan Liu, Rebiguli Aji, Xiangjun Meng, Wei‐Qiang Gao, Li Li

“…The IECs were isolated for RNA sequencing and chromatin immunoprecipitation sequencing to identify molecular signalling pathways and key molecules leading to IBD in mice. …”
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