Article
Oncology
Fengjuan Fan, Stefano Malvestiti, Sonia Vallet, Judith Lind, Jose Manuel Garcia-Manteiga, Eugenio Morelli, Qinyue Jiang, Anja Seckinger, Dirk Hose, Hartmut Goldschmidt, Andreas Stadlbauer, Chunyan Sun, Heng Mei, Martin Pecherstorfer, Latifa Bakiri, Erwin F. Wagner, Giovanni Tonon, Martin Sattler, Yu Hu, Pierfrancesco Tassone, Dirk Jaeger, Klaus Podar
Summary: This study demonstrates a significant correlation between JunB and angiogenic factors in MM, independent of hypoxia. JunB plays a dual role as a mediator of MM cell survival, proliferation, drug resistance, and also promotes angiogenesis in the BM microenvironment. These findings suggest targeting JunB as a potential strategy in MM therapy.
Article
Multidisciplinary Sciences
Bjoern Klabunde, Andre Wesener, Wilhelm Bertrams, Isabell Beinborn, Nicole Paczia, Kristin Surmann, Sascha Blankenburg, Jochen Wilhelm, Javier Serrania, Kevin Knoops, Eslam M. Elsayed, Katrin Laakmann, Anna Lena Jung, Andreas Kirschbaum, Sven Hammerschmidt, Belal Alshaar, Nicolas Gisch, Mobarak Abu Mraheil, Anke Becker, Uwe Voelker, Evelyn Vollmeister, Birke J. Benedikter, Bernd Schmeck
Summary: This study reveals that the dysregulation of the NAD(+) salvage pathway upon Streptococcus pneumoniae infection promotes bacterial replication, while NAD(+) treatment inhibits its growth. Additionally, increasing NAD(+) production reduces bacterial replication and exerts antibacterial effects by affecting bacterial metabolism.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Manon Watzky, Solene Huard, Ludmila Juricek, Julien Dairou, Caroline Chauvet, Xavier Coumoul, Anne Letessier, Benoit Miotto
Summary: This study reveals that the metabolic enzyme HK2, which fuels cancer cell growth, is a transcriptional target and modulator of AHR. In addition, high HK2 expression and low AHR methylation in tumors are associated with a worse overall survival in patients.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Fabio Zani, Julianna Blagih, Tim Gruber, Michael D. Buck, Nicholas Jones, Marc Hennequart, Clare L. Newell, Steven E. Pilley, Pablo Soro-Barrio, Gavin Kelly, Nathalie M. Legrave, Eric C. Cheung, Ian S. Gilmore, Alex P. Gould, Cristina Garcia-Caceres, Karen H. Vousden
Summary: Artificial sweeteners, calorie-free substitutes for sugar, are widely used in many food products. However, concerns have been raised about the long-term safety of consuming certain sweeteners. This study shows that high doses of sucralose can have immunomodulatory effects, limiting T cell proliferation and differentiation, affecting membrane order, T cell receptor signaling, and intracellular calcium mobilization. Mice given sucralose showed decreased T cell responses in cancer and bacterial infection models, as well as reduced T cell function in autoimmune models. These findings suggest that sucralose intake can dampen T cell-mediated responses, which may be useful in treating T cell-dependent autoimmune disorders.
Article
Oncology
Islam Alshamleh, Nina Kurrle, Philipp Makowka, Raj Bhayadia, Rahul Kumar, Sebastian Suesser, Marcel Seibert, Damian Ludig, Sebastian Wolf, Sebastian E. Koschade, Karoline Stoschek, Johanna Kreitz, Dominik C. Fuhrmann, Rosa Toenges, Marco Notaro, Federico Comoglio, Jan Jacob Schuringa, Tobias Berg, Bernhard Bruene, Daniela S. Krause, Jan-Henning Klusmann, Thomas Oellerich, Frank Schnuetgen, Harald Schwalbe, Hubert Serve
Summary: In this study, the influence of FLT3-ITD on AML metabolism was investigated, and it was found that FLT3-ITD induces the expression of PDP1, enhancing oxidative glucose metabolism and drug resistance. The results suggest that PDP1 may be a targetable vulnerability in the management of AML.
Review
Pharmacology & Pharmacy
Noelia Diaz-Morales, Eva M. Baranda-Alonso, Carlos Martinez-Salgado, Francisco J. Lopez-Hernandez
Summary: Hypertension is a complex disorder resulting from changes in the pressure-natriuresis relationship and increased sympathetic tone. External factors affecting sodium handling in the kidneys can disrupt this relationship. It is important to understand the interplay between the sympathetic nervous system and the pressure-natriuresis mechanism in the development of hypertension.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Julie M. Garlick, Steven M. Sturlis, Paul A. Bruno, Joel A. Yates, Amanda L. Peiffer, Yejun Liu, Laura Goo, LiWei Bao, Samantha N. De Salle, Giselle Tamayo-Castillo, Charles L. Brooks, Sofia D. Merajver, Anna K. Mapp
Summary: Inhibitors of transcriptional protein-protein interactions have high value for both tools and therapeutic applications. This study demonstrates that norstictic acid, a depsidone natural product, blocks Med25-transcriptional activator PPIs through an alternative binding site, providing opportunities for inhibitor discovery in challenging proteins with structurally dynamic loops.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Biochemistry & Molecular Biology
Yuanqiang Ma, Gyurim Lee, Su-Young Heo, Yoon-Seok Roh
Summary: This review summarizes the relationship between oxidative stress and the development of nonalcoholic fatty liver disease (NAFLD), and discusses the potential role of antioxidants as therapeutic agents for NAFLD.
Article
Biochemistry & Molecular Biology
Azra Memon, Yuliya Pyao, Yerin Jung, Hwa-Sik Choi, Ki-Duk Song, Woon Kyu Lee
Summary: The JunB site, but not the Sp1 sites, at the mKlf10 promoter is essential for the basal transcriptional activity of the gene, as revealed by luciferase reporter assays and EMSA.
Article
Multidisciplinary Sciences
Sang Jun Han, Prashi Jain, Yosef Gilad, Yan Xia, Nuri Sung, Mi Jin Park, Adam M. Dean, Rainer B. Lanz, Jianming Xu, Clifford C. Dacso, David M. Lonard, Bert W. O'Malley
Summary: It was found that SRC-3 is highly expressed in regulatory T cells (Tregs) and B cells, indicating its important role in Treg function regulation. By using a genetically engineered tamoxifen-inducible Treg-cell-specific SRC-3 knockout (KO) mouse, it was observed that breast tumors and prostate cancer were permanently eradicated without autoimmune side effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Ji Hye Han, Wook Kim
Summary: The review highlights the role of peripheral CB1R in metabolic inflammation and its involvement in various metabolic disorders such as insulin resistance. It also discusses the therapeutic potential of second- and third-generation peripherally restricted CB1R antagonists for treating obesity-induced metabolic inflammation without causing central CB1R-mediated neurobehavioral effects.
Article
Biochemistry & Molecular Biology
Young-Im Kim, Yu-Chou Tseng, Gamze Ayaz, Shasha Wang, Hualong Yan, Wendy du Bois, Howard Yang, Tao Zhen, Maxwell P. P. Lee, Paul Liu, Rosandra N. Kaplan, Jing Huang
Summary: This study identifies SOX9 as a critical transcription factor induced by RUNX2 in osteosarcoma cells. The activation of MYC, a downstream target of RUNX2, is mediated by SOX9. The interaction between SOX9 and chromatin factor JMJD1C is also demonstrated, showing that depletion of JMJD1C impairs osteosarcoma tumor growth.
CELL AND BIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
You Duan, Qiangxiang Zhang, Yanxin Jiang, Wanting Zhang, Yingyin Cheng, Mijuan Shi, Xiao-Qin Xia
Summary: This article introduces developmental research on grass carp based on a high-quality transcriptome. By collecting and analyzing samples at multiple time points, the study explores the role of lncRNAs and alternative splicing in fish development and identifies a family of short interspersed elements that are preferentially expressed during early zygotic activation and their possible regulatory components. Furthermore, the study investigates the changes in retained intron alternative splicing events during zygotic activation and tissue differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Iqra Bashir Nehvi, Neha Quadir, Mohd Khubaib, Javaid Ahmad Sheikh, Mohd Shariq, Krishnaveni Mohareer, Sharmistha Banerjee, Syed Asad Rahman, Nasreen Z. Ehtesham, Seyed E. Hasnain
Summary: Mycobacterium tuberculosis ArgD plays a crucial role in amino acid biosynthetic pathways and can be a potential drug target for tuberculosis treatment due to its metabolic regulatory functions.
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Yingdong Deng, Simin Tang, Jiurong Cheng, Xiangsheng Zhang, Danqin Jing, Ziqiang Lin, Jun Zhou
Summary: The dorsal root ganglion (DRG) plays an active role in the development of neuropathic pain (NP), but its mechanism in NP regulation is not fully understood. The immune system has been increasingly recognized as important in the pathogenesis of NP, particularly through immune-related genes (IRGs) and specific immune cells. However, the involvement of IRGs in DRG and their regulation of NP action has not been fully elucidated.
Article
Cell Biology
E. Evonne Jean, Olivia Good, Juan M. Inclan Rico, Heather L. Rossi, De'Broski R. Herbert
Summary: Communication between the nervous and immune systems at mucosal barrier sites, particularly the respiratory tract, plays a crucial role in protecting host immunity, sensing and responding to various stimuli to induce airway inflammation. Neuropeptides and neurotransmitters have been found to regulate immune cell responses and influence type 2 immunity in the airway.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Immunology
Kirstin Aschbacher, Steve Cole, Melissa Hagan, Luisa Rivera, Alyssa Baccarella, Owen M. Wolkowitz, Alicia F. Lieberman, Nicole R. Bush
Summary: This study found that pre-treatment pro-inflammatory imbalance can predict the treatment response to antidepressants in trauma-exposed mothers and their young children, with the imbalance being related to the severity of PTSD and depression symptoms.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Review
Biochemistry & Molecular Biology
Heather L. Rossi, Jorge F. Ortiz-Carpena, Devon Tucker, Andrew E. Vaughan, Nilam S. Mangalmurti, Noam A. Cohen, De'Broski R. Herbert
Summary: This review discusses the important role of TFF family members in healthy and diseased airways. TFF peptides maintain and restore homeostasis in the airways through their regulation of the mucous layer, cell motility, cell differentiation, and immune function. Differences in TFF member tracks between humans and mice pose a challenge for research. New evidence suggests that TFF proteins interact with receptor binding partners in mediating biological effects in mouse models of repair and infection. TFF peptides may be reasonable therapeutic targets in the treatment of airway diseases.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Editorial Material
Immunology
De'Broski Herbert, Irene Salinas, Eugene M. Oltz
JOURNAL OF IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Samuel Cole Kitzman, Tingting Duan, Miles A. Pufall, Pamela K. Geyer
Summary: The nuclear lamina (NL) is an extensive protein network that regulates chromatin organization and gene expression. Lap2-emerin-MAN1 domain (LEM-D) proteins, key members of the NL, connect the NL to the genome through interactions with Barrier-to-Autointegration Factor (BAF). In this study, the contributions of emerin and BAF to gene expression in the ovary were investigated. The results revealed a set of NL-regulated genes, most of which were found to be dependent on the activation of Checkpoint kinase 2 (Chk2). Additionally, a smaller set of emerin-dependent genes were identified. These findings shed light on the importance of NL proteins in gene expression regulation and have implications for NL-associated diseases.
G3-GENES GENOMES GENETICS
(2022)
Article
Microbiology
Fungai Musaigwa, Severin Donald Kamdem, Thabo Mpotje, Paballo Mosala, Nada Abdel Aziz, De'Broski R. Herbert, Frank Brombacher, Justin Komguep Nono
Summary: Schistosomiasis is a potentially lethal parasitic disease that impairs vaccine-induced immunity. This study found that chronic Schistosoma mansoni infection hinders the persistence of vaccine specific antibody responses in humans and mice, and the removal of parasites can partially restore vaccine-induced memory responses. The findings emphasize the importance of reducing schistosomiasis burden before vaccination.
Article
Medicine, Research & Experimental
Kazuya Masuda, Adam Kornberg, Jonathan Miller, Sijie Lin, Nathan Suek, Theo Botella, Kerim A. Secener, Alyssa M. Bacarella, Liang Cheng, Matthew Ingham, Vilma Rosario, Ahmed M. Al-Mazrou, Steven A. Lee-Kong, Ravi P. Kiran, Marlon Stoeckius, Peter Smibert, Armando Del Portillo, Paul E. Oberstein, Peter A. Sims, Kelley S. Yan, Arnold Han
Summary: This study identified distinct subsets of T cells in colorectal cancer, including cytotoxic T cells associated with good outcomes (GZMK(+)KLRG1(+)) and dysfunctional cytotoxic T cells associated with poor outcomes (GNLY(+)CD103(+)). Additionally, CD38(+) Tregs were associated with bad outcomes and inhibitory effects on antitumor immunity. These findings suggest the potential utility of these T cell subsets in predicting outcomes and the possibility of novel therapies targeting specific T cell populations.
Article
Biochemistry & Molecular Biology
Swarna Bais, Abigail Norwillo, Gordon Ruthel, De'Broski R. Herbert, Bruce D. Freedman, Robert M. Greenberg
Summary: Schistosomiasis, caused by parasitic flatworms, is a neglected tropical disease. Current treatment options face challenges, highlighting the need for alternative targets. This study identifies the role of TRPML channels in parasite neuromuscular activity and tegumental integrity, making them potential drug targets for combating schistosomiasis.
Article
Parasitology
Masmudur M. Rahman, Grant McFadden, Gordon Ruthel, De' Broski. R. Herbert, Bruce D. Freedman, Robert M. Greenberg, Swarna Bais
Summary: The study demonstrates that Myxoma virus can infect and replicate in schistosomes, causing damage to the parasites. This suggests that Myxoma virus could potentially serve as a new and safe class of anthelmintic therapeutics.
EXPERIMENTAL PARASITOLOGY
(2022)
Article
Multidisciplinary Sciences
Craig M. Rush, Zannel Blanchard, Jacob T. Polaski, Kyle S. Osborne, Krystle Osby, Jeffery M. Vahrenkamp, Chieh-Hsiang Yang, David H. Lum, Christy R. Hagan, Kimberly K. Leslie, Miles A. Pufall, Kristina W. Thiel, Jason Gertz
Summary: The novel endometrioid endometrial cancer cell line model, HCI-EC-23, retains estrogen receptor expression and responds to estrogen and progesterone induction. It exhibits similar molecular characteristics to the commonly studied Ishikawa cell line and can be used to study the hormonal aspects of endometrial cancer.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Zachery Mielko, Yuning Zhang, Harshit Sahay, Yiling Liu, Matthew A. Schaich, Brittani Schnable, Abigail M. Morrison, Debbie Burdinski, Sheera Adar, Miles Pufall, Bennett Van Houten, Raluca Gordan, Ariel Afek
Summary: Somatic mutations are highly concentrated at transcription factor binding sites, particularly in melanomas with UV-induced mutations. The inefficient repair of UV lesions within TF-binding sites is proposed as one of the main mechanisms for this hypermutation pattern due to competition between TFs and DNA repair proteins. However, the impact of UV irradiation on TF binding to DNA and whether TFs maintain specificity for their DNA sites after UV exposure remain unclear. Using a high-throughput approach called UV-Bind, researchers found that UV lesions significantly altered the DNA binding preferences of all tested TFs, with a decrease in binding specificity. Despite the overall reduction in DNA-binding specificity, TFs can still compete with repair proteins for lesion recognition, consistent with their specificity for UV-irradiated DNA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Rebecca A. Lee, Maggie Chang, Nicholas Yiv, Ariel Tsay, Sharon Tian, Danielle Li, Coralie Poulard, Michael R. Stallcup, Miles A. Pufall, Jen-Chywan Wang
Summary: The classical dogma of glucocorticoid-induced insulin resistance states that it is caused by the activation of certain genes. However, this study shows that glucocorticoids can also stimulate the expression of insulin-sensitizing genes. The transcriptional co-regulator EHMT2 plays a key role in this process, as it is involved in the induction of Irs2 to restrict the extent of insulin resistance caused by glucocorticoids.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Agathe Marcelot, Felipe Rodriguez-Tirado, Philippe Cuniasse, Mei-ling Joiner, Simona Miron, Alexey A. Soshnev, Mimi Fang, Miles A. Pufall, Katherine D. Mathews, Steven A. Moore, Sophie Zinn-Justin, Pamela K. Geyer
Summary: Barrier-to-autointegration factor (BAF) is an essential component of the nuclear lamina that regulates gene expression, cell cycle progression, and nuclear integrity. A dominant pathogenic BAF variant, Gly16Arg, has been identified in a patient with progressive neuromuscular weakness, causing changes in chromatin structure and nuclear functions. This study demonstrates how a missense mutation can alter protein conformation and lead to a dominant disease phenotype.
Article
Microbiology
Babatunde Adewale, Hammed Mogaji, Joshua Balogun, Emmanuel Balogun, Francisca Olamiju, De'Broski Herbert
Summary: Nigeria, particularly the Borgu region, has seen a significant decline of 51.9% in soil-transmitted helminthiases (STH) infection since 2013. However, the lack of access to latrine facilities and the prevalence of walking barefoot among children remain concerning. The prevalence of STH infection is associated with community, age, and parental occupation.
Article
Immunology
Adam Kornberg, Theo Botella, Christine S. S. Moon, Samhita Rao, Jared Gelbs, Liang Cheng, Jonathan Miller, Alyssa M. M. Bacarella, Javier A. A. Garcia-Vilas, Justin Vargas, Xuechen Yu, Izabela Krupska, Erin Bush, Reuben Garcia-Carrasquillo, Benjamin Lebwohl, Suneeta Krishnareddy, Suzanne Lewis, Peter H. R. Green, Govind Bhagat, Kelley S. S. Yan, Arnold Han
Summary: Celiac disease (CD) is an autoimmune disease characterized by intestinal inflammation triggered by dietary gluten. This study conducted single-cell analysis of T cells in the intestine and peripheral blood of CD patients in different disease states. The results showed that CD was associated with activated intestinal T cells, including follicular T helper cells, regulatory T cells, and natural killer cell receptor-expressing T cells. After gluten ingestion, cytotoxic T cells in CD were mobilized along with gluten-specific CD4(+) T cells. These findings suggest a rapid response of cytotoxic T cells in CD after gluten exposure.
SCIENCE IMMUNOLOGY
(2023)