Article
Chemistry, Multidisciplinary
Guangyan Du, Jie Jiang, Qibiao Wu, Nathaniel J. Henning, Katherine A. Donovan, Hong Yue, Jianwei Che, Wenchao Lu, Eric S. Fischer, Nabeel Bardeesy, Tinghu Zhang, Nathanael S. Gray
Summary: DGY-09-192 is a potential prototype FGFR degrader with high selectivity, preferentially inducing degradation of FGFR1 and 2 while sparing FGFR3 and 4. In clinically relevant models, DGY-09-192 demonstrated the ability to degrade FGFR2 fusion proteins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Acoustics
Weiye Xiu, Xin Wang, Zhiguo Na, Shiyou Yu, Jingyang Wang, Mengyuan Yang, Yongqiang Ma
Summary: This study investigated the impact of different ultrasound durations on the structure and bioactivity of sweet corncob polysaccharides. Findings showed that ultrasound-assisted degradation significantly reduced the molecular weight of the polysaccharides while maintaining their basic structure. In vivo experiments demonstrated that 60 minutes of ultrasound treatment effectively controlled blood glucose levels in mice with type 2 diabetes by regulating glycolipid metabolism, reducing inflammation and oxidative stress levels, and inhibiting disaccharide activity in the small intestine.
ULTRASONICS SONOCHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Jianrong Yang, Jingtao Zhong, Mi Zhou, Yinghong Zhou, Peng Xiu, Feng Liu, Fuhai Wang, Zelun Li, Yuntian Tang, Yuanyuan Chen, Siyang Yao, Tao Huang, Tianqi Liu, Xiaofeng Dong
Summary: T7 peptide inhibits endothelial cell proliferation, migration, and tube formation, and promotes apoptosis under different oxygen conditions via integrin α3β1 and αvβ3 pathways. The combination of T7 peptide and meloxicam enhances the anti-tumor effect against HCC tumors.
Article
Chemistry, Analytical
Sang Jun Park, Myoung Ki Cho, Dong Joon Lee, Deuk Hwa Song, Chang Su Lim, Choong-Kyun Noh, Dong Min Lee, Kyeong Sook Choi, Sung Jae Shin, Hwan Myung Kim
Summary: A two-photon probe SCX was developed to reflect the level of COX-2 in colorectal cancer patients and distinguish between cancerous and normal tissue. In vitro and cell imaging studies showed that SCX could effectively differentiate the expression levels of COX-2 in cancerous and normal cells.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Pharmacology & Pharmacy
Camilo Torres, Simon Dumas, Valentina Palacio-Castaneda, Stephanie Descroix, Roland Brock, Wouter P. R. Verdurmen
Summary: This study developed a mathematical model to evaluate approaches towards cytosolic protein delivery, focusing on solid cancer tissues. The analysis highlighted the importance of optimizing protein design and tuning receptor affinity to enhance therapeutic potential. Results also showed how enzymatic cargoes can improve therapeutic activity even at low catalytic rates, indicating that the goal of cytosolic protein delivery for therapeutic effects is within reach with current protein engineering approaches.
Article
Plant Sciences
Devesh Tewari, Pawan Gupta, Sweta Bawari, Archana N. Sah, Davide Barreca, Maryam Khayatkashani, Hamid Reza Khayat Kashani
Summary: The study demonstrated for the first time the significant analgesic activity of Ficus palmata L. fruit extract, and highlighted the potential of the plant chemicals rutin and psoralen in ameliorating painful conditions.
Article
Engineering, Environmental
Bo Wang, Jianjie Gao, Jing Xu, Xiaoyan Fu, Hongjuan Han, Zhenjun Li, Lijuan Wang, Fujian Zhang, Yongsheng Tian, Rihe Peng, Quanhong Yao
Summary: This study successfully reconstructed degradation pathways for 3-chlorocatechol (3CC) and 4-chlorocatechol (4CC) through genetic engineering, demonstrating the ability of engineered bacteria to metabolize these aromatic compounds. The research provides a new approach for constructing pollution remediation-engineered bacteria, with potential applications in dealing with complex organic hazardous materials.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Meghan E. Garrett, Jared Galloway, Helen Y. Chu, Hannah L. Itell, Caitlin Stoddard, Caitlin R. Wolf, Jennifer K. Logue, Dylan McDonald, Frederick A. Matsen, Julie Overbaugh
Summary: This study used the Phage-DMS approach to define antibody escape profiles to the SARS-CoV-2 S protein in COVID-19 convalescent plasma. It found common antibody binding regions but variable escape mutations within these regions, as well as individual variation in less commonly targeted epitopes. This suggests potential individual variation in antibody-mediated virus evolution.
Review
Cell Biology
Ron Benyair, Avital Eisenberg-Lerner, Yifat Merbl
Summary: The Golgi apparatus plays a central role in cellular protein trafficking and signaling, with its structure and function tightly coupled and dynamically changing in health and disease. Recent studies have revealed various mechanisms by which the Golgi apparatus degrades aberrant proteins, including autophagy, retrograde trafficking to the ER, and Golgi apparatus-related degradation.
Article
Immunology
Gowhar Ali, Nazar Ul Islam, Muhammad Qaim, Rahim Ullah, Muhammad Saeed Jan, Khadija Shabbiri, Muhammad Shafique, Muhammad Ayaz
Summary: This study evaluated the efficacy of 2-hydroxybenzohydrazide (HBH) as a drug against pyrexia, inflammation, and nociception, as well as its therapeutic effects on oxidative stress and C-reactive proteins. The findings showed that HBH dose-dependently inhibited pain, inflammation, and pyrexia, and had significant anti-nociceptive, anti-inflammatory, and antipyretic activities involving opioidergic mechanism. Computational studies also revealed HBH's affinity for the COX-I/II target receptors.
INFLAMMOPHARMACOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Vitor L. Molosse, David A. B. Pereira, Fernanda Rigon, Kalista E. Loregian, Elaine Magnani, Marcos I. Marcondes, Renata H. Branco, Pedro D. B. Benedeti, Eduardo M. Paula
Summary: Scientists are seeking techniques to improve animal-feed utilization, and this study focused on increasing the rumen undegradable protein (RUP) content of cottonseed meal through different heating methods and xylose treatment. The results showed that the evaluated processing methods can increase cottonseed meal RUP. Further studies are needed to confirm the findings and assess the effects on ruminal fermentation parameters, animal performance, and economic viability.
Article
Biology
Sumana Sharma, Toby Whitehead, Mateusz Kotowski, Emily Zhi Qing Ng, Joseph Clarke, Judith Leitner, Yi-Ling Chen, Ana Mafalda Santos, Peter Steinberger, Simon J. Davis
Summary: This study used CRISPR-based genome screening and Jurkat cell-based transcriptional reporter assay to investigate the signaling pathways of T-cell activation and inhibition. The results confirmed the utility of arrayed and pooled screens in studying different mediators. SHP2 was identified as the major PD-1-specific, SH2 family mediator of inhibitory signaling.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Jinmin Miao, Yunpeng Bai, Yiming Miao, Zihan Qu, Jiajun Dong, Ruo-Yu Zhang, Devesh Aggarwal, Brenson A. Jassim, Quyen Nguyen, Zhong-Yin Zhang
Summary: In this study, a novel series of proteolysis targeting chimeras (PROTACs) were designed and synthesized to achieve efficient degradation of SHP2 both inside the cell and in vivo. Compound P9 showed improved anti-tumor activity and led to nearly complete tumor regression in a xenograft mouse model by depleting SHP2 and suppressing phospho-ERK1/2 in the tumor.
Article
Chemistry, Medicinal
Daiki Takahashi, Taiichi Ora, Shigekazu Sasaki, Naoki Ishii, Toshio Tanaka, Takumi Matsuda, Mutsuki Ikeda, Jun Moriyama, Nobuo Cho, Hiroshi Nara, Hironobu Maezaki, Masahiro Kamaura, Kenichiro Shimokawa, Hirokazu Arimoto
Summary: Targeted protein degradation is a promising drug discovery approach, with the ubiquitin-proteasome system being the most studied. Autophagy, another degradation system, has the potential for targeted degradation but is still in the early stages. Previous research identified the first autophagy-based degraders, autophagy-targeted chimeras (AUTACs), which showed a relationship between guanine modification of cysteine residues and selective autophagy. This study examined the importance of the cysteine substructure in AUTACs and demonstrated significant improvements in activity by replacing cysteine with other moieties.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Yu Ding, Dong Xing, Yiyan Fei, Boxun Lu
Summary: Targeted protein degradation (TPD) provides unprecedented opportunities for drug discovery. PROTACs technology has already entered clinical trials and changed the landscape of small-molecule drugs. In addition to PROTACs, new degrader technologies harnessing alternative degradation machineries, especially lysosomal pathways, have emerged and broadened the spectrum of degradable targets.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Medicine, Research & Experimental
Di Chen, Elizabeth D. Hughes, Thomas L. Saunders, Jiangping Wu, Magda N. Hernandez Vasquez, Taija Makinen, Philip D. King
Summary: This study demonstrates that RASA1 and EPHB4 function in the same signaling pathway to protect against the development of CM-AVM, independent of physical interaction. These findings have important implications for possible treatment of this disease.
Article
Public, Environmental & Occupational Health
Bin Ni, Erin Gettler, Rebecca Stern, Heather M. Munro, Mark Steinwandel, Melinda C. Aldrich, Debra L. Friedman, Maureen Sanderson, David Schlundt, David M. Aronoff, Deepak K. Gupta, Martha J. Shrubsole, Loren Lipworth
Summary: Disruptions to healthcare during the COVID-19 pandemic were primarily driven by health system-initiated deferrals and individual perceptions of COVID-19 risk, disproportionately affecting different population groups.
JOURNAL OF PUBLIC HEALTH RESEARCH
(2022)
Article
Endocrinology & Metabolism
Caitlin Resendes, Daniel J. Horan, Alexander G. Robling, Benlian Gao, Ginger L. Milne, Matthew L. Warman
Summary: Serotonin has been found to have effects on bone, but the correlation between blood serotonin levels and bone mass is still unclear. Recent study shows that administering serotonin to mice with low serotonin levels can restore intestinal motility and bone mass, but whether it directly affects bone metabolism or indirectly affects metabolism by improving intestinal function needs further research.
Article
Environmental Sciences
Jarrod L. Eaton, Amber L. Cathey, Jennifer A. Fernandez, Deborah J. Watkins, Monica K. Silver, Ginger L. Milne, Carmen Velez-Vega, Zaira Rosario, Jose Cordero, Akram Alshawabkeh, John D. Meeker
Summary: This study aims to investigate the impact of glyphosate and its primary environmental degradate, AMPA, on oxidative stress in pregnant women. It found that an increase in urinary AMPA concentration was associated with higher levels of certain oxidative stress biomarkers, while the association with glyphosate was weaker.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Public, Environmental & Occupational Health
Jordan R. Kuiper, Katie M. O'Brien, Barrett M. Welch, Emily S. Barrett, Ruby H. N. Nguyen, Sheela Sathyanarayana, Ginger L. Milne, Shanna H. Swan, Kelly K. Ferguson, Jessie P. Buckley
Summary: The study shows that different dilution-adjustment methods can be used when combining urinary biomarker data with different measures of urinary dilution, and these methods yield comparable and comparable results.
Article
Nutrition & Dietetics
Yong-Moon Mark Park, Jenna Lilyquist, Thomas J. Van't Erve, Katie M. O'Brien, Hazel B. Nichols, Ginger L. Milne, Clarice R. Weinberg, Dale P. Sandler
Summary: Plasma carotenoids, as well as supplemental beta-carotene, were found to be associated with lower concentrations of 8-iso-PGF(2 alpha) metabolite. These associations may reflect antioxidant effects.
EUROPEAN JOURNAL OF NUTRITION
(2022)
Article
Clinical Neurology
Stephen Bruehl, Frederic T. Billings, Sara Anderson, Gregory Polkowski, Andrew Shinar, Jonathan Schildcrout, Yaping Shi, Ginger Milne, Anthony Dematteo, Puneet Mishra, R. Norman Harden
Summary: This study evaluated the preoperative predictors of complex regional pain syndrome (CRPS) outcomes following total knee arthroplasty (TKA) at 6 months. The findings suggest that central sensitization and inflammatory mechanisms play a role in CRPS risk after tissue trauma.
Article
Anesthesiology
Stephen Bruehl, Ginger Milne, Jonathan Schildcrout, Yaping Shi, Sara Anderson, Andrew Shinar, Gregory Polkowski, Puneet Mishra, Frederic T. Billings
Summary: Total knee arthroplasty (TKA) is effective for pain reduction in most patients, but 15% or more report unsatisfactory long-term pain outcomes. Elevated perioperative oxidative stress (OS) seems to exert small but significant adverse effects on long-term post-TKA pain outcomes, although this OS seems unrelated to ischemic reperfusion (IR) injury associated with extended tourniquet use.
Article
Biochemistry & Molecular Biology
Felicia Kuperwaser, Gal Avital, Michelle J. Vaz, Kristen N. Noble, Allison N. Dammann, Tara M. Randis, David M. Aronoff, Adam J. Ratner, Itai Yanai
Summary: Group B Streptococcus (GBS) is a pathobiont that ascends to the placenta and causes adverse pregnancy outcomes by producing the toxin beta-hemolysin/cytolysin (beta-h/c). This study shows that GBS modulates the state of innate immune cells by subverting host inflammation through beta-h/c, leading to worse outcomes.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yingya Zhao, Marina S. Nogueira, Ginger L. Milne, Xingyi Guo, Hui Cai, Qing Lan, Nathaniel Rothman, Qiuyin Cai, Yu-Tang Gao, Qingxia Chen, Xiao-Ou Shu, Gong Yang
Summary: The study found that miRNAs associated with F2-IsoP-M are enriched for various lipid peroxidation-related processes, and some miRNAs exhibited functional interactions with mRNAs involved in the regulation of beta-oxidation.
Article
Multidisciplinary Sciences
Yuki Matsushita, Jialin Liu, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Mizuki Nagata, Yuki Arai, Wanida Ono, Kouhei Yamamoto, Thomas L. Saunders, Joshua D. Welch, Noriaki Ono
Summary: This study discovered a new class of skeletal stem cells in the bone marrow's endosteal space, which are abundant in young bone marrow, express Fgfr3, and have osteoblastic-chondrocytic transitional identities. These cells can transform into cells that generate bone tumors.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Yang Zhao, Guizhen Zhao, Ziyi Chang, Tianqing Zhu, Ying Zhao, Haocheng Lu, Chao Xue, Thomas L. Saunders, Yanhong Guo, Lin Chang, Y. Eugene Chen, Jifeng Zhang
Summary: To achieve specific and efficient smooth muscle cell (SMC) targeted gene deletion, we used CRISPR/Cas9-mediated homologous recombination to generate Cre-knockin mice by inserting CreNLSP2A or CreERT2-P2A sequences into the homologous arm surrounding the translation start site of the Myh11 gene. We evaluated the efficiency, specificity, tamoxifen-dependent controllability, and functionality of Cre-mediated recombination in both sexes using reporter mice. These models will expand the research toolbox and facilitate unbiased and comprehensive research in SMCs and SMC-dependent cardiovascular diseases.
Article
Multidisciplinary Sciences
Joshua Soto Ocana, Nile U. Bayard, Jessica L. Hart, Audrey K. Thomas, Emma E. Furth, D. Borden Lacy, David M. Aronoff, Joseph P. Zackular
Summary: Clostridioides difficile damages the colonic mucosa through potent exotoxins. The factors contributing to C. difficile pathogenesis are not fully understood, but likely involve ecological, immune, and environmental factors. Recent studies have shown that nonsteroidal anti-inflammatory drugs exacerbate C. difficile infection, although the mechanism behind this is unclear.
Article
Biochemistry & Molecular Biology
Yingya Zhao, Ginger L. Milne, Qingxia Chen, Qi Dai, Xianglan Zhang, Marina S. Nogueira, Hui Cai, Qing Lan, Nathaniel Rothman, Qiuyin Cai, Yu-Tang Gao, Xiao-Ou Shu, Wei Zheng, Gong Yang
Summary: This study prospectively evaluated the association between lipid peroxidation and the incidence of type 2 diabetes (T2D) in a sample of women. The results showed that higher levels of F-2-IsoPs in urine were associated with an increased risk of T2D, especially among women with higher BMI.
FREE RADICAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
P. Challa Anup, Xinnan Niu, Etoi A. Garrison, Sara L. Van Driest, Lisa M. Bastarache, Ethan S. Lippmann, Robert R. Lavieri, Jeffery A. Goldstein, David M. Aronoff
Summary: Pregnant people have been systematically excluded from clinical trials, resulting in a lack of safety data for common drugs. This study used electronic health records to investigate the effects of maternal exposure to different drugs on neurodevelopmental defects in their children, and proposed an agile framework for improving medication regulations.
COMMUNICATIONS MEDICINE
(2022)