Article
Biochemistry & Molecular Biology
Mirva J. Saaranen, Heli Alanen, Kirsi E. H. Salo, Emmanuel Nji, Pekka Karkkainen, Constanze Schmotz, Lloyd W. Ruddock
Summary: Proteins in the thioredoxin superfamily, such as protein disulfide isomerase (PDI) and glutaredoxins, have similar structures and catalytic mechanisms. PDI uses glutathione for oxidation/reduction in vitro, while glutaredoxins have a high affinity for glutathione. Mutating the active site of PDI to a more glutaredoxin-like motif increases its reactivity with glutathione.
Review
Biochemistry & Molecular Biology
Carlos Santos-Martin, Geqing Wang, Pramod Subedi, Lilian Hor, Makrina Totsika, Jason John Paxman, Begona Heras
Summary: The DsbA enzyme, as part of the disulfide bond forming system, plays a crucial role in bacterial virulence factor assembly and is a potential target for new virulence blockers. Despite extensive studies on DSB systems in various bacterial species, little is known about how DsbA oxidoreductases recognize and interact with a wide range of substrates.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Oncology
Haimeng Yan, Donghua He, Jianwei Qu, Yang Liu, Ruyi Xu, Huiyao Gu, Jing Chen, Yi Li, Enfan Zhang, Yi Zhao, Jingsong He, Zhen Cai
Summary: IL-32 is highly expressed in relapsed MM patients and is associated with infiltration of M2 M phi. IL-32γ promotes M phi-mediated MM cell protection and induces polarization of M2 M phi partly through increasing CSF1 expression. These findings provide a crucial theoretical basis for targeted M phi immunotherapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Sheyda Bahiraii, Martin Brenner, Fangfang Yan, Wolfram Weckwerth, Elke H. Heiss
Summary: This study reveals that sulforaphane (Sfn) inhibits the expression of proinflammatory markers in M1 macrophages and enhances cellular energy levels. By impeding the function of pyruvate kinase M2 (PKM2), Sfn alters the glycolytic activity and IL-1β expression in macrophages, thus influencing the inflammatory response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Attila Andor, Mahendravarman Mohanraj, Zsuzsanna Anna Pato, Katalin Uri, Beata Biri-Kovacs, Qing Cheng, Elias S. J. Arner
Summary: TXNL1 has dual functions, acting as a supporting factor for TrxR1-driven redox activities in disulfide reduction reactions and functioning as an ATP-independent chaperone.
Article
Biochemistry & Molecular Biology
Shayna L. Vicker, Eran N. Maina, Abigail K. Showalter, Nghi Tran, Emma E. Davidson, Morgan R. Bailey, Stephen W. McGarry, Wilson M. Freije, James D. West
Summary: Thioredoxins, key oxidant defense enzymes, show variability in the active site motif in newly sequenced genomes, posing a challenge in determining functional genes. Mutagenesis experiments reveal that thioredoxin is less tolerant of substitutions at conserved tryptophan and proline, highlighting a noteworthy plasticity within this critical enzyme.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Peisi Liao, Chunmao He
Summary: This study documents a highly optimized synthesis method for the Sec-to-Cys homologue of human selenoprotein F, and elucidates the disulfide pairing mode of SelF. The research not only lays the foundation for the synthesis of natural selenoproteins, but also provides important insights into the structure of the SelF domain.
FRONTIERS IN CHEMISTRY
(2021)
Article
Immunology
Armand O. Brown, Kavindra Singh, Melissa R. Cruz, Karan Gautam Kaval, Liezl E. Francisco, Barbara E. Murray, Danielle A. Garsin
Summary: Enterococcus faecalis can form cardiac microlesions during severe infection, with DsbA protein playing a key role in virulence and microlesion formation. Additionally, the bacterium promotes cardiomyocyte death and modulates proinflammatory cytokine levels, contributing to the immune response suppression.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Wenxiao Li, Xiaowen Xin, Xiujun Li, Jianli Geng, Yunfu Sun
Summary: The study revealed that miR-27a-3p derived from M2 macrophages promotes cancer stemness of HCC by downregulating TXNIP, leading to increased proliferation, drug resistance, migration, invasion, and in vivo tumorigenicity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Anja Kolbinger, Tim J. Schaeufele, Hanna Steigerwald, Joschua Friedel, Sandra Pierre, Gerd Geisslinger, Klaus Scholich
Summary: This study investigates the development and maintenance of inflammatory microenvironments during Toll-like receptor 2-mediated paw inflammation. It is found that immune cells are organized into three zones, including a pathogen-containing core region, a proinflammatory region, and an anti-inflammatory region. Eosinophils present in all three regions adapt their cytokine profile and their depletion affects resolution of inflammation.
EMBO MOLECULAR MEDICINE
(2023)
Article
Engineering, Biomedical
Min Zou, Jiachen Sun, Zhou Xiang
Summary: The hydrogel loaded with IL-4 and BMP-2 shows promising effects in reducing inflammation, promoting macrophage M2-type differentiation, and enhancing bone regeneration after implantation, offering a potential strategy for future bone tissue engineering applications.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Xiangxu Wei, Miao Zhong, Song Wang, Lexun Li, Zi-Long Song, Junmin Zhang, Jianqiang Xu, Jianguo Fang
Summary: The study synthesized 72 disulfides and identified two compounds with significant antitumor activity against HeLa cells. Kinetic studies showed one of the disulfides had faster inhibition of Trx compared to the other. These findings suggest potential for the development of anticancer candidates with Trx inhibition.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hiba Abu Hariri, Ilana Braunstein, Talal Salti, Fabian Glaser, Tal Gefen, Naama Geva-Zatorsky, Tamar Ziv, Moran Benhar
Summary: This study characterized the dynamic cysteine proteome of human macrophages and identified the role of thiol redox control in regulating inflammatory responses. The findings provide insights into the adaptability of macrophages to changing inflammatory and redox environments.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Multidisciplinary Sciences
Kai Xiong, Jia Deng, Tinghui Yue, Wenting Hu, Xinglin Zeng, Tao Yang, Tianbao Xiao
Summary: This study aimed to investigate the anti-inflammatory and immune-modulatory roles of berberine (BBR) in ulcerative colitis (UC) treatment, and to explore the underlying mechanisms. The results showed that BBR suppressed M1 macrophages while promoting M2 macrophages, which contributed to its anti-inflammatory and immune-modulating activities.
Article
Biochemistry & Molecular Biology
Maria Rynikova, Petra Adamkova, Petra Hradicka, Jana Stofilova, Denisa Harvanova, Jana Matejova, Vlasta Demeckova
Summary: There are two main types of macrophages, inflammatory (M1) and anti-inflammatory (M2) macrophages. In vitro polarization of monocytic cell lines using various stimuli can produce these cells. Currently, there is no consensus on the best method for obtaining reliable M1 and M2 macrophages from the THP-1 cell line. This study compared three different polarization protocols at the transcriptomic level and found that M1 macrophages polarized using PMA and IFN-gamma along with LPS had the highest expression of M1-associated regulatory genes and cytokines and chemokines.
Article
Immunology
Katharine S. Walter, Eugene Kim, Renu Verma, Jonathan Altamirano, Sean Leary, Yuan J. Carrington, Prasanna Jagannathan, Upinder Singh, Marisa Holubar, Aruna Subramanian, Chaitan Khosla, Yvonne Maldonado, Jason R. Andrews
Summary: This study found that there is limited genetic diversity among SARS-CoV-2 samples from the same household, while individuals infected with the same viral strain from different households have lower genetic similarity. Shared within-host variations in a household are significantly associated with household membership. However, current sequencing and bioinformatic workflows may not consistently detect low-frequency within-host variants.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Public, Environmental & Occupational Health
Sara Naseri, Yael Rosenberg-Hasson, Holden T. T. Maecker, Maria I. I. Avrutsky, Paul D. D. Blumenthal
Summary: This pilot study investigated the potential of measuring cytokines in menstrual effluent and compared the cytokine profiles of menstrual versus peripheral blood. The results showed a tenuous correlation between menstrual effluent and peripheral blood cytokine profiles, with higher levels detected in menstrual effluent for many cytokines. Further studies are needed to evaluate the relationship between peripheral and menstrual blood cytokines in broader populations.
HEALTH SCIENCE REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Katarina M. Guzman, Dillon P. Cogan, Krystal L. Brodsky, Alexander M. Soohoo, Xiuyuan Li, Natalia Sevillano, Irimpan I. Mathews, Khanh P. Nguyen, Charles S. Craik, Chaitan Khosla
Summary: This study discovered and characterized two F(ab) antibodies (AC2 and BB1) that potently inhibit the catalytic activity of the ketosynthase-acyltransferase (KS-AT) core of Module 2 in the synthesis of 6-deoxyerythronolide B synthase (DEBS). The antibodies were found to modulate ACP-mediated reactions catalyzed by Module 2 through different mechanisms. Another F(ab) antibody, AA5, was identified to bind to the KS-AT fragment of DEBS Module 2 without altering any parameter, similar to a previously characterized antibody, 1B2, which primarily recognizes the N-terminal helical docking domain of DEBS Module 3. Crystal structures of AA5 and 1B2 bound to the KS-AT fragment of Module 2 were solved, revealing distinct recognition features of the two antibodies. These findings provide valuable tools and insights for understanding the structure-function relationships of DEBS Module 2, one of the most well-studied modules of an assembly line polyketide synthase (PKS).
Article
Immunology
Joseph E. Levitt, Haley Hedlin, Sophie Duong, Di Lu, Justin Lee, Bryan Bunning, Nadia Elkarra, Benjamin A. Pinsky, Eileen Heffernan, Eric Springman, Richard B. Moss, Hector F. Bonilla, Julie Parsonnet, Roham T. Zamanian, Jamison J. Langguth, Jenna Bollyky, Chaitan Khosla, Mark R. Nicolls, Manisha Desai, Angela J. Rogers
Summary: The study aimed to evaluate the effectiveness of Acebilustat in treating outpatients with COVID-19, and the results showed that the medication did not shorten symptom duration.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Biochemical Research Methods
Hilary L. Zetlen, Kevin T. Cao, Kevin D. Schichlein, Noelle Knight, Holden T. Maecker, Kari C. Nadeau, Meghan E. Rebuli, Mary B. Rice
Summary: This study compared the detection of proteins in nasal epithelial lining fluid (NELF) across three different protein analysis platforms. Results showed good correlation among most proteins, but inconsistent results for low abundance proteins. Among the three platforms, MSD had the highest sensitivity for analyte detection.
JOURNAL OF IMMUNOLOGICAL METHODS
(2023)
Article
Multidisciplinary Sciences
Meng Yu, Afandi Charles, Alberto Cagigi, Wanda Christ, Bjoern osterberg, Sara Falck-Jones, Lida Azizmohammadi, Eric ahlberg, Ryan Falck-Jones, Julia Svensson, Mu Nie, Anna Warnqvist, Fredrika Hellgren, Klara Lenart, Rodrigo Arcoverde Cerveira, Sebastian Ols, Gustaf Lindgren, Ang Lin, Holden Maecker, Max Bell, Niclas Johansson, Jan Albert, Christopher Sundling, Paulo Czarnewski, Jonas Klingstroem, Anna Faernert, Karin Lore, Anna Smed-Soerensen
Summary: Effective humoral immune responses require well-coordinated interactions between B and T follicular helper (Tfh) cells. This study found that during COVID-19 infection, the number of SARS-CoV-2-specific circulating Tfh (cTfh) cells expands with disease severity. The frequency of SARS-CoV-2-specific cTfh cells correlates with plasmablast frequencies and the levels of SARS-CoV-2 antibodies. However, the development of virus-specific cTfh cells is delayed in patients with severe disease, leading to delayed induction of high-avidity neutralizing antibodies.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Sumanth Mosale Seetharam, Yi Liu, Jason Wu, Lenn Fechter, Kanagavel Murugesan, Holden Maecker, Jason Gotlib, James Zehnder, Ramasamy Paulmurugan, Anandi Krishnan
Summary: Impaired protein homeostasis plays a significant role in myeloproliferative neoplasms (MPNs). This study identifies the downregulation of enkurin (ENKUR) and the upregulation of CDC20 as potential markers of MPN pathogenesis, suggesting a novel role for ENKUR in MPNs.
Article
Cell Biology
Joann Diray-Arce, Slim Fourati, Naresh Doni Jayavelu, Ravi Patel, Cole Maguire, Ana C. Chang, Ravi Dandekar, Jingjing Qi, Brian H. Lee, Patrick van Zalm, Andrew Schroeder, Ernie Chen, Anna Konstorum, Anderson Brito, Jeremy P. Gygi, Alvin Kho, Jing Chen, Shrikant Pawar, Ana Silvia Gonzalez-Reiche, Annmarie Hoch, Carly E. Milliren, James A. Overton, Kerstin Westendorf, Charles B. Cairns, Nadine Rouphael, Steven E. Bosinger, Seunghee Kim-Schulze, Florian Krammer, Lindsey Rosen, Nathan D. Grubaugh, Harm van Bakel, Michael Wilson, Jayant Rajan, Hanno Steen, Walter Eckalbar, Chris Cotsapas, Charles R. Langelier, Ofer Levy, Matthew C. Altman, Holden Maecker, Ruth R. Montgomery, Elias K. Haddad, Rafick P. Sekaly, Denise Esserman, Al Ozonoff, Patrice M. Becker, Alison D. Augustine, Leying Guan, Bjoern Peters, Steven H. Kleinstein, IMPACC Network
Summary: The IMPACC cohort study analyzed more than 1,000 hospitalized COVID-19 patients and identified five illness trajectory groups. By performing deep immunophenotyping and utilizing 14 distinct assays, the study revealed cellular and molecular signatures that differentiate moderate from severe and fatal COVID-19 cases within 72 hours of hospital admission. Importantly, these signatures also distinguish patients with different disease outcomes, such as recovery or progression to fatal outcomes, within 28 days. The study highlights the potential of characterizing immune responses to inform clinical prognosis and interventions.
CELL REPORTS MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Florian Wimmers, Allison R. Burrell, Yupeng Feng, Hong Zheng, Prabhu S. Arunachalam, Mengyun Hu, Sara Spranger, Lindsay E. Nyhoff, Devyani Joshi, Meera Trisal, Mayanka Awasthi, Lorenza Bellusci, Usama Ashraf, Sangeeta Kowli, Katherine C. Konvinse, Emily Yang, Michael Blanco, Kathryn Pellegrini, Gregory Tharp, Thomas Hagan, R. Sharon Chinthrajah, Tran T. Nguyen, Alba Grifoni, Alessandro Sette, Kari C. Nadeau, David B. Haslam, Steven E. Bosinger, Jens Wrammert, Holden T. Maecker, Paul J. Utz, Taia T. Wang, Surender Khurana, Purvesh Khatri, Mary A. Staat, Bali Pulendran
Summary: This study used a multi-omics approach to investigate immunity to SARS-CoV2 in infants and young children. The results showed that infants mounted a robust mucosal immune response and had long-lasting antibody titers.
Article
Biochemistry & Molecular Biology
Tamara D. Simon, Sabrina Sedano, Yael Rosenberg-Hasson, Ramon Durazo-Arvizu, Kathryn B. Whitlock, Paul Hodor, Jason S. Hauptman, David D. Limbrick, Patrick McDonald, Jeffrey G. Ojemann, Holden T. Maecker
Summary: This study compares cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. The results showed lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery in the children who went on to require multiple surgeries.
Article
Chemistry, Multidisciplinary
Elise Loppinet, Harrison A. Besser, Christina E. E. Lee, Wei Zhang, Bianxiao Cui, Chaitan Khosla
Summary: Protein dysregulation is a common cause of various diseases. Targeted protein degradation is a promising therapeutic approach for proteins without easily druggable pockets or catalytic sites. This study presents the synthesis and validation of heterobifunctional molecules that bind to a target protein via a small molecule ligand and deliver it to the lysosome using a short gluten peptide. The results demonstrate the effective endocytosis and degradation of representative secreted, cell surface, and transmembrane proteins. Optimizing these prototype molecules could lead to pharmacologically relevant LYTAC agents.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Sharon S. Newman, Brandon D. Wilson, Daniel Mamerow, Benjamin C. Wollant, Hnin Nyein, Yael Rosenberg-Hasson, Holden T. Maecker, Michael Eisenstein, H. Tom Soh
Summary: The current methods for quantifying the human plasma proteome are limited to a small range compared to the actual range. The authors propose a tuning approach for proximity-based assays that allows simultaneous quantification of multiple analytes across a wide concentration range. This method has the potential to greatly improve precision medicine by accurately describing patient physiology.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Shreya Kishore, Chaitan Khosla
Summary: By mining genomic data from the NCBI database, this study presents an updated catalogue of 8799 non-redundant assembly line polyketide synthase clusters across 4083 species, showing a threefold increase in the past 4 years. Furthermore, 95% of the clusters are 'orphan clusters' with no known chemical or biological characterization. These findings suggest that the diversity of assembly line PKSs remains largely unexplored and highlight the potential of genomics-driven approaches for natural product discovery.
Review
Allergy
Sayantani B. Sindher, Andrew R. Chin, Nima Aghaeepour, Lawrence Prince, Holden Maecker, Gary M. Shaw, David K. Stevenson, Kari C. Nadeau, Michael Snyder, Purvesh Khatri, Scott D. Boyd, Virginia D. Winn, Martin S. Angst, R. Sharon Chinthrajah
Summary: The prevalence of food allergy is increasing globally, causing significant safety, economic, and emotional burdens. However, identifying patients who would benefit from preventive strategies is challenging due to the heterogeneity of allergy trajectories and clinical phenotypes. Further studies are needed to investigate the molecular mechanisms that differentiate these trajectories and drive food allergy development. Omics approaches have the potential to provide insights into these mechanisms, but their application in food allergy research is still in its early stages.
FRONTIERS IN ALLERGY
(2023)
Article
Biochemistry & Molecular Biology
Elise Loppinet, Harrison A. Besser, Agnele Sylvia Sewa, Fu-Chen Yang, Bana Jabri, Chaitan Khosla
Summary: Celiac disease is caused by gluten-derived antigens triggering inflammation through presenting to CD4+ T cells. In this study, we propose a mechanism for the deamidation and concentration of gluten peptides in the lysosomes of antigen-presenting cells, which explains the high concentration of gluten peptides required for an inflammatory response in CeD patients. We found that a ternary complex formed between a gluten peptide, transglutaminase-2 (TG2), and a2-macroglobulin, which was endocytosed by LRP-1. The covalent TG2-peptide adduct underwent endolysosomal decoupling, resulting in the expected deamidated epitope. Our findings suggest a pathogenic role for dendritic cells and/or macrophages in CeD and implicate TG2 in the lysosomal clearance of unwanted proteins.
CELL CHEMICAL BIOLOGY
(2023)