Article
Biochemical Research Methods
Natascha Goedecke, Sabrina Herrmann, Viola Weichelt, Dagmar Wirth
Summary: Synthetic expression cassettes enable control of transgene expression in animal models, and their performance is influenced by chromosomal integration sites and epigenetic status. In this study, the effect of UCOE HNRPA2B1-CBX3 and its subfragments on doxycycline-controlled expression modules was investigated. Results showed that CBX3 facilitated expression and supported external control, suggesting a strategy for overcoming epigenetic constraints and enabling transgene expression in mice.
ACS SYNTHETIC BIOLOGY
(2023)
Review
Neurosciences
Martin Stacho, Denise Manahan-Vaughan
Summary: The retrosplenial cortex is a crucial brain structure for spatial navigation and memory, generating diverse neuronal properties and playing an important role in spatial cognition. It supports goal-directed navigation by integrating idiothetic cues, spatial relations, and environmental features. Additionally, its mnemonic functions suggest a possible involvement in autobiographical information storage.
TRENDS IN NEUROSCIENCES
(2022)
Article
Cell Biology
Wanli Zhang, Weikuan Sun, Xiaofan Gu, Chunxiao Miao, Lixing Feng, Qiang Shen, Xuan Liu, Xiongwen Zhang
Summary: This study demonstrates the important role of GDF-15 in the induction of muscle atrophy in tumor-derived exosomes, and supports the possibility of targeting GDF-15 for the treatment of cancer cachexia.
CELL DEATH DISCOVERY
(2022)
Review
Oncology
Tingting Ling, Jing Zhang, Fuwan Ding, Lanlan Ma
Summary: GDF15 is a cytokine associated with anorexia, weight loss, and cancer cachexia. It is highly expressed during tissue injury, inflammation, oxidative stress, and cancer. GDF15 plays a significant role in the development of cancer cachexia, and its regulatory mechanisms need further investigation.
Article
Multidisciplinary Sciences
Zuzana Cierna, Bozena Smolkova, Dana Cholujova, Paulina Gronesova, Svetlana Miklikova, Marina Cihova, Jana Plava, Michal Mego
Summary: This study found that high PD-L1 expression in breast cancer patients is associated with shorter progression-free survival, as well as low circulating levels of VEGF, TNF-beta and IL-15. Multivariate analysis showed that patients with low VEGF levels had an increased risk of PD-L1 overexpression. Plasma cytokines could potentially serve as non-invasive biomarkers for identifying high-risk breast cancer cases.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Jingwei Sun, Qiao Lu, Miguel F. Sanmanmed, Jun Wang
Summary: Immunomodulatory agents targeting the PD-1/PD-L1 pathway have shown success in cancer treatment, but resistance remains a challenge. The identification of Siglec-15 as a potential immune suppressor offers a new avenue for immunotherapy, particularly in patients resistant to anti-PD-1/PD-L1 therapy.
CLINICAL CANCER RESEARCH
(2021)
Article
Microbiology
Maya Shemesh, Turgut E. Aktepe, Joshua M. Deerain, Julie L. McAuley, Michelle D. Audsley, Cassandra T. David, Damian F. J. Purcell, Victoria Urin, Rune Hartmann, Gregory W. Moseley, Jason M. Mackenzie, Gideon Schreiber, Daniel Harari
Summary: Type I interferons play a crucial role in combating viral infections, yet SARS-CoV-2 virus has evolved to disrupt immune defenses by blocking IFN beta production through six genes. Despite reducing pSTAT1 levels, the virus still activates antiviral programs and remains sensitive to added interferon, presenting a therapeutic opportunity.
Article
Multidisciplinary Sciences
Hannah K. Jaeger, David A. Davis, Ashwin Nair, Prabha Shrestha, Alexandra Stream, Amulya Yaparla, Robert Yarchoan
Summary: Epstein-Barr virus (EBV) downregulates immune surface markers to avoid immune recognition. Pomalidomide (Pom) was shown to increase immune surface marker expression in EBV-infected tumor cells. The mechanisms by which Pom leads to these effects in EBV-infected cells were explored.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Joana Esteves de Lima, Cedrine Blavet, Marie-Ange Bonnin, Estelle Hirsinger, Glenda Comai, Laurent Yvernogeau, Marie-Claire Delfini, Lea Bellenger, Sebastien Mella, Sonya Nassari, Catherine Robin, Ronen Schweitzer, Claire Fournier-Thibault, Thierry Jaffredo, Shahragim Tajbakhsh, Frederic Relaix, Delphine Duprez
Summary: A fibroblast population undergoes myoblast conversion in response to BMP signaling and contributes nuclei to myotubes at the myotendinous junction, controlling limb muscle patterning. This challenges the traditional view that limb muscle cells originate from somites and connective tissue fibroblasts derive from lateral plate mesoderm.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Jeffrey Alan Tomalka, Adam Nicolas Pelletier, Slim Fourati, Muhammad Bilal Latif, Ashish Sharma, Kathryn Furr, Kevin Carlson, Michelle Lifton, Ana Gonzalez, Peter Wilkinson, Genoveffa Franchini, Robert Parks, Norman Letvin, Nicole Yates, Kelly Seaton, Georgia Tomaras, Jim Tartaglia, Merlin L. Robb, Nelson L. Michael, Richard Koup, Barton Haynes, Sampa Santra, Rafick Pierre Sekaly
Summary: Understanding the mechanism of vaccine efficacy is crucial for developing next-generation vaccines. The study suggests that activation of CREB1 by RV144 HIV-1 vaccine enhances adaptive immunity, leading to reduced HIV-1 acquisition. This finding highlights the importance of CREB1 signaling in efficacious HIV-1 vaccines.
Article
Cell Biology
Kristina Johansson, John D. Gagnon, Simon K. Zhou, Marlys S. Fassett, Andrew W. Schroeder, Robin Kageyama, Rodriel A. Bautista, Hewlett Pham, Prescott G. Woodruff, K. Mark Ansel
Summary: The miR-15/16 family plays a crucial role in regulating the cell cycle, memory formation, and survival of T cells. Decreased miR-15/16 levels upon T cell activation allow for the expansion of effector T cells. In regulatory T cells (Tregs), miR-15/16 are essential for maintaining immune tolerance by controlling the expression of critical proteins. Loss of miR-15/16 in Tregs leads to impaired immune suppression and the development of inflammation.
Article
Microbiology
Aayushi Uberoi, Casey Bartow-McKenney, Qi Zheng, Laurice Flowers, Amy Campbell, Simon A. B. Knight, Neal Chan, Monica Wei, Victoria Lovins, Julia Bugayev, Joseph Horwinski, Charles Bradley, Jason Meyer, Debra Crumrine, Carrie Hayes Sutter, Peter Elias, Elizabeth Mauldin, Thomas R. Sutter, Elizabeth A. Grice
Summary: This research demonstrates the essential role of the skin microbiome in regulating skin barrier formation and repair, mediated by microbiota signaling through the aryl hydrocarbon receptor (AHR) in keratinocytes. These findings reveal a fundamental mechanism whereby the microbiota influences the integrity of the skin barrier.
CELL HOST & MICROBE
(2021)
Article
Immunology
Young Joon Choi, Hoyoung Lee, Jong Hoon Kim, So-Young Kim, June-Young Koh, Moa Sa, Su-Hyung Park, Eui-Cheol Shin
Summary: This study demonstrates that human memory CD8(+) T cells in advanced stages of differentiation respond better to IL-15, with CD5 expression level correlating strongly with IL-15 hyporesponsiveness. CD5 suppresses IL-15-induced proliferation of human memory CD8(+) T cells by inhibiting the mTOR pathway.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell Biology
Shinya Abe, Takuma Asahi, Takahiro Hara, Guangwei Cui, Akihiro Shimba, Shizue Tani-ichi, Kohei Yamada, Kazuko Miyazaki, Hitoshi Miyachi, Satsuki Kitano, Naotoshi Nakamura, Junichi Kikuta, Alexis Vandenbon, Masaki Miyazaki, Ryo Yamada, Toshiaki Ohteki, Masaru Ishii, Veronika Sexl, Takashi Nagasawa, Koichi Ikuta
Summary: This study reveals that hematopoietic cells, particularly monocytes and dendritic cells, are the cellular source of IL-15 for NK cell development in the bone marrow. Additionally, it demonstrates that BM NK cells are localized in scattered and clustered compartments, suggesting distinct functions in the immune response.
Review
Pathology
Sonia Arely Garcia, Vincent Y. Ng, Masahiro Iwamoto, Motomi Enomoto-Iwamoto
Summary: Osteochondromas are the most common benign bone tumor in children, causing issues such as skeletal deformity and pain. Surgery is currently the only treatment option. Mouse models have been developed to study the pathology and origin of osteochondromas, with research focusing on potential therapeutic drugs.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Oncology
Katherine C. Kurnit, Ashley Draisey, Rebecca C. Kazen, Christine Chung, Luan H. Phan, Jerry B. Harvey, Jiping Feng, SuSu Xie, Russell R. Broaddus, Jessica L. Bowser
Summary: The loss of CD73 in endometrial carcinomas shifts the activity of TGF-beta from tumor suppressor to promoter, affecting cell functions and invasiveness.
Editorial Material
Oncology
Michael Leung, Jane E. Rogers, Imad Shureiqi
Summary: Delayed severe toxicities may occur in patients with heterozygous DPYD mutation genotypes, particularly those of African descent and female sex, after exposure to fluoropyrimidine. Treatment with uridine triacetate should not be restricted to patients with early-onset fluoropyrimidine toxicities or homozygous DPYD mutations.
CLINICAL COLORECTAL CANCER
(2021)
Review
Oncology
Daoyan Wei, Liang Wang, Xiangsheng Zuo, Robert S. Bresalier
Summary: Pancreatic cancer has a poor prognosis and increasing incidence, necessitating novel intervention strategies. Vitamin D shows promise in reducing the risk and improving survival of pancreatic cancer, as well as regulating stromal reprogramming and immune response, providing opportunities for intervention.
Article
Oncology
Peiying Yang, Xiangsheng Zuo, Shailesh Advani, Bo Wei, Jessica Malek, Rena Sue Day, Imad Shureiqi
Summary: This study evaluated potential predictive biomarkers for celecoxib chemopreventive activity in patients with FAP. Our findings demonstrated the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical chemopreventive response in patients with FAP.
CANCER PREVENTION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Shivanand Pudakalakatti, Mark Titus, Jose S. Enriquez, Sumankalai Ramachandran, Niki M. Zacharias, Imad Shureiqi, Yi Liu, James C. Yao, Xiangsheng Zuo, Pratip K. Bhattacharya
Summary: Peroxisome proliferator-activated receptor delta (PPARD) plays an essential role in cell metabolism, cell proliferation, inflammation, and tumorigenesis. This study investigated the metabolic changes regulated by PPARD in gastric tumor development. The findings suggest that PPARD overexpression leads to alterations in metabolite levels, particularly in inosine monophosphate, uracil, phenylalanine, glycine, isocitrate, inosine, adenosine monophosphate, UDP-glucose, and oxypurinol. Additionally, fatty acid oxidation was identified as a potential bioenergy source for PPARD-expressing gastric tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Maya Hassane, Zahraa Rahal, Nareg Karaoghlanian, Jiexin Zhang, Ansam Sinjab, Justin W. Wong, Wei Lu, Paul Scheet, J. Jack Lee, Maria Gabriela Raso, Luisa M. Solis, Junya Fujimoto, Hassan Chami, Alan L. Shihadeh, Humam Kadara
CANCER PREVENTION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Marta Kapalczynska, Manqiang Lin, Jeroen Maertzdorf, Julian Heuberger, Stefanie Muellerke, Xiangsheng Zuo, Ramon Vidal, Imad Shureiqi, Anne-Sophie Fischer, Sascha Sauer, Hilmar Berger, Evelyn Kidess, Hans-Joachim Mollenkopf, Frank Tacke, Thomas F. Meyer, Michael Sigal
Summary: This study reveals the interaction between Helicobacter pylori infection and gastric epithelial stem cells and their stromal niche. The differentiation of gastric epithelial stem cells is regulated by subsets of stromal cells. H. pylori infection disrupts the BMP feedback loop, leading to stem cell self-renewal and accumulation of gland base cells.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Yi Liu, Yasunori Deguchi, Daoyan Wei, Fuyao Liu, Micheline J. Moussalli, Eriko Deguchi, Donghui Li, Huamin Wang, Lovie Ann Valentin, Jennifer K. Colby, Jing Wang, Xiaofeng Zheng, Haoqiang Ying, Mihai Gagea, Baoan Ji, Jiaqi Shi, James C. Yao, Xiangsheng Zuo, Imad Shureiqi
Summary: PPARδ signaling pathway plays a key role in the progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC), inducing an immunosuppressive microenvironment through the upregulation of CCL2, driving the disease progression.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Jayashri Ghosh, Bryant M. Schultz, Joe Chan, Claudia Wultsch, Rajveer Singh, Imad Shureiqi, Stephanie Chow, Ahmet Doymaz, Sophia Varriano, Melissa Driscoll, Jennifer Muse, Frida E. Kleiman, Konstantinos Krampis, Jean-Pierre J. Issa, Carmen Sapienza
Summary: Non-genetic predisposition to colorectal cancer is difficult to measure accurately, hindering targeted prevention and screening efforts. Epigenetic changes in the normal mucosa of colorectal cancer patients can be used as a tool to predict outcomes. A distinct subgroup of normally-appearing mucosa with disrupted DNA methylation, known as the Outlier Methylation Phenotype (OMP), was identified in colorectal cancer patients. These OMP patients showed altered gene expression and microbial dysbiosis. The findings have implications for prevention and prognosis in colorectal cancer.
CANCER PREVENTION RESEARCH
(2022)
Article
Oncology
Imad Shureiqi
Summary: Further data from the ASPREE trial raises concerns about the use of aspirin for colorectal cancer prevention in elderly subjects. A 95-variant colorectal cancer polygenic risk score failed to identify the subset of elderly individuals who could have benefited from aspirin preventive activity. Further research is needed to define predictive biomarkers for aspirin preventive activity. Meanwhile, the efficacy of aspirin for colorectal cancer prevention in the elderly becomes more questionable.
CANCER PREVENTION RESEARCH
(2022)
Article
Oncology
Ming Zhao, Timothy P. P. DiPeri, Maria Gabriela Raso, Xiaofeng Zheng, Yasmeen Qamar Rizvi, Kurt W. W. Evans, Fei Yang, Argun Akcakanat, Marco Roberto Estecio, Debu Tripathy, Ecaterina E. E. Dumbrava, Senthil Damodaran, Funda Meric-Bernstam
Summary: Research shows that increasing TROP2 expression can enhance the activity of TROP2 antibody drug conjugates (ADCs). In certain breast cancers, downregulating the transcription factor ZEB1 can increase the expression of E-cad and TROP2, making cancer cells more sensitive to TROP2 ADCs such as sacituzumab govitecan (SG). The demethylating agent decitabine decreases DNA methyltransferase expression and TROP2 promoter methylation, leading to increased TROP2 expression. Treatment with decitabine and overexpression of TROP2 significantly enhance the antitumor activity of SG.
Article
Medicine, Research & Experimental
Hua Wang, Rohan Moniruzzaman, Lei Li, Baoan Ji, Yi Liu, Xiangsheng Zuo, Reza Abbasgholizadeh, Jun Zhao, Guangchao Liu, Ruiqi Wang, Hongli Tang, Ryan Sun, Xiaoping Su, Tse-Hua Tan, Anirban Maitra, Huamin Wang
Summary: This study reveals the crucial role of HPK1 in acinar-to-ductal metaplasia (ADM) and the progression of pancreatic intraepithelial neoplasias (PanINs). HPK1 interacts with and phosphorylates RasGAP to inhibit Ras activity and downstream signaling, regulating acinar cell plasticity. Loss of HPK1 kinase activity promotes an immunosuppressive tumor microenvironment and accelerates the progression of PanINs to pancreatic ductal adenocarcinoma (PDAC).
JOURNAL OF CLINICAL INVESTIGATION
(2023)