Review
Cell Biology
Katie Treasure, James Harris, Gary Williamson
Summary: Dysregulation of innate immune responses can lead to chronic inflammatory conditions. Glucocorticoids are effective but come with serious side effects. Sulforaphane, derived from plants of the brassica family, has shown potential as an alternative therapy due to its induction of detoxification enzymes and anti-inflammatory properties. It may also have steroid-sparing activity, making it a promising adjunctive treatment. Further research is needed to fully understand its clinical applications.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Caroline Swoboda, Lena Deloch, Claudia von Zimmermann, Tanja Richter-Schmidinger, Bernd Lenz, Johannes Kornhuber, Christiane Muehle
Summary: This study investigated the potential of MIF at genetic, expression, and protein levels as a risk factor and biomarker for diagnosing, monitoring, or predicting MDD. The results suggest a genetic effect of MIF in women but do not provide strong evidence for its utility as a biomarker for MDD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Krishnamoorthi Sumaiya, Charles Solomon Akino Mercy, Gangatharan Muralitharan, Abdurahman Hajinur Hirad, Abdullah A. Alarfaj, Kalimuthusamy Natarajaseenivasan
Summary: This study evaluated the diagnostic value of macrophage migration inhibitory factor (MIF) for leptospirosis. The results showed that serum MIF levels were significantly elevated in leptospirosis patients and correlated with disease severity and progression. Serum MIF exhibited high sensitivity and specificity, making it a potential rapid diagnostic marker for leptospirosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rosario Caltabiano, Rocco De Pasquale, Eliana Piombino, Giorgia Campo, Ferdinando Nicoletti, Eugenio Cavalli, Katia Mangano, Paolo Fagone
Summary: Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease with unknown etiology and immunoinflammatory origin. Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) may play key roles in autoimmune diseases and certain forms of cancers. The expression of MIF and DDT in normal skin and DLE lesions varies, suggesting a potential protective role in skin inflammation.
Article
Immunology
Krishnamoorthi Sumaiya, Panneerselvam Selvambika, Kalimuthusamy Natarajaseenivasan
Summary: This study identified an anti-inflammatory drug, ibu-dilast, as a potential MIF inhibitor for the treatment of leptospirosis. In vitro and in vivo experiments showed that ibu-dilast could reduce inflammation and protect against lethality caused by leptospiral infection.
MICROBIAL PATHOGENESIS
(2022)
Article
Multidisciplinary Sciences
Jianbo He, Lin Zheng, Xiaojuan Li, Furong Huang, Sitao Hu, Lei Chen, Manya Jiang, Xianfeng Lin, Haibo Jiang, Yifan Zeng, Tianshen Ye, Dingkun Lin, Qian Liu, Jiake Xu, Kai Chen
Summary: This study aimed to explore the therapeutic potential of Obacunone (OB) on osteoporosis and its rudimentary mechanisms. In vitro and in vivo experiments showed that OB suppressed the formation and function of osteoclasts. Mechanistically, OB interacted with macrophage migration inhibitory factor (MIF), attenuating receptor activator of nuclear factor kappa B (NF-KB) ligand (RANKL)-induced signaling pathways. This led to a decrease in the expression level of the master transcriptional factor of osteoclastogenesis, nuclear factor of activated T cells 1 (NFATc1), and its downstream osteoclast-specific proteins. OB also alleviated estrogen deficiency-induced osteoporosis by targeting MIF and inhibiting hyperactive osteoclasts.
JOURNAL OF ADVANCED RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Chunfang Zan, Bishan Yang, Markus Brandhofer, Omar El Bounkari, Jurgen Bernhagen
Summary: This article reviews the similarities and differences between macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT), focusing on their structures, signaling pathways, and roles in diseases. The article emphasizes the differential activities of MIF and MIF-2 in various diseases and discusses potential future opportunities for targeting both homologs.
Article
Cardiac & Cardiovascular Systems
Yan-yan Li, Hui Wang, Yang-yang Zhang
Summary: The MIF gene rs755622 G/C polymorphism is significantly associated with CAD, especially in the Chinese population. Individuals carrying the C allele of the MIF gene rs755622 G/C polymorphism may have a higher susceptibility to CAD.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Chemistry, Analytical
Chenwen Shao, Christian Hedberg, Yong Qian
Summary: A novel activity-based probe, TPP2, was reported for direct labeling and imaging of endogenous MIF activity within live cells and in a mouse model of liver cancer. TPP2 allows for the dynamic monitoring of intracellular MIF activity and the identification of liver cancer with high sensitivity and selectivity, providing a promising new imaging approach for elucidating MIF-related biological functions in liver cancer.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zhangping Xiao, Shanshan Song, Deng Chen, Ronald van Merkerk, Petra E. van Der Wouden, Robbert H. Cool, Wim J. Quax, Gerrit J. Poelarends, Barbro N. Melgert, Frank J. Dekker
Summary: The development of a MIF-targeted PROTAC, MD13, is able to induce MIF degradation at low concentrations and suppress the proliferation of inflammatory and cancer cells, demonstrating the potential therapeutic value of PROTACs in cancer treatment.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Immunology
Xiangwen Shi, Yipeng Wu, Haonan Ni, Mingjun Li, Baochuang Qi, Yongqing Xu
Summary: The expression level of macrophage migration inhibitory factor (MIF) is upregulated in osteomyelitis patients and cell models. MIF inhibits osteogenic differentiation by activating the NF-κB signaling pathway. The study demonstrates that the MIF inhibitor iSO-1 and MIF knockdown can reverse the inhibitory effect of inflammation on osteogenic differentiation, providing a potential target for osteomyelitis treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Ni Cui, Hui Li, Yaoshan Dun, Jeffrey W. Ripley-Gonzalez, Baiyang You, Dezhao Li, Yuan Liu, Ling Qiu, Cui Li, Suixin Liu
Summary: This study found that hepatocyte-expressed macrophage migration inhibitory factor (MIF) can limit the occurrence of fatty liver during obesity. Exercise can reduce lipotoxicity and inhibit JNK activation by modulating endogenous hepatic MIF in nonalcoholic fatty liver disease (NAFLD). These findings have important clinical implications for the prevention and intervention of NAFLD induced by immoderate diet.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Benjamin L. Woolbright, Ganeshkumar Rajendran, Erika Abbott, Austin Martin, Sarah Amalraj, Katie Dennis, Xiaogang Li, Joshua Warrick, John A. Taylor
Summary: MIF2 functions similarly to MIF1 in promoting bladder cancer development and progression, partly through CD74. Dual inhibition of MIF homologs is more effective in reducing tumor burden in bladder cancer compared to single inhibition of MIF1.
JOURNAL OF PATHOLOGY
(2023)
Article
Chemistry, Analytical
Andrew Parkins, Suzanne I. Sandin, Jonathon Knittel, Andreas H. Franz, Jianhua Ren, Eva de Alba, Georgios Pantouris
Summary: This study reveals the impact of impurities in 4-hydroxyphenyl pyruvate (4-HPP) on the enzymatic activity of macrophage migration inhibitory factor (MIF) and the determination of MIF inhibitor values. The findings provide a tool for designing error-free in vitro and in vivo experiments.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zhangping Xiao, Deng Chen, Fabian Mulder, Shanshan Song, Petra E. Wouden, Robbert H. Cool, Barbro N. Melgert, Gerrit J. Poelarends, Frank J. Dekker
Summary: This study reported the development and application of a new probe 8 for the selective labeling of macrophage migration inhibitory factor (MIF) and its homolog MIF2, facilitating research on their roles in cancer and other diseases.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Medicinal
Jimin Hwang, Natalie Strange, Rami Mazraani, Matthew J. Phillips, Allan B. Gamble, Wilhelmina M. Huston, Joel D. A. Tyndall
Summary: A new series of CtHtrA inhibitors were developed by proline ring expansion and Cg-substitutions, which showed significantly improved antichlamydial activity in vitro.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Emma Spencer, Patrice Rosengrave, Jonathan Williman, Geoff Shaw, Anitra C. Carr
Summary: Protein carbonyls concentrations increased in critically ill patients with septic shock, and patients with pneumonia had significantly higher protein carbonyl concentrations compared to other sources of sepsis. Vitamin C intervention did not attenuate the increase in protein carbonyls.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Jimin Hwang, Sonya Mros, Allan B. Gamble, Joel D. A. Tyndall, Arlene McDowell
Summary: Nanoparticle drug delivery systems offer a promising approach to address limitations of antimicrobial drugs. Controlled engineering of nanoparticle size using microfluidic technology can significantly improve drug delivery optimization.
Article
Biochemistry & Molecular Biology
Anitra C. Carr, Emma Spencer, Helen Heenan, Helen Lunt, Monica Vollebregt, Timothy C. R. Prickett
Summary: This study found that body weight is a significant predictor of vitamin C status in patients with diabetes, suggesting that those with higher body weight may require more vitamin C than average.
Article
Microbiology
Yasmeen N. Ruma, Mikhail V. Keniya, Joel D. A. Tyndall, Brian C. Monk
Summary: The study characterized the wild type C. parapsilosis CYP51 and its resistance-causing point mutation Y132F, revealing increased resistance to fluconazole and voriconazole with the Y132F mutation. The research provides insights into the susceptibility of recombinant CYP51 from C. parapsilosis to azole drugs, which may help advance structure-directed antifungal discovery.
Article
Chemistry, Medicinal
Nicole M. R. McNeil, Eric W. J. Gates, Neda Firoozi, Nicholas J. Cundy, Jessica Leccese, Sarah Eisinga, Joel D. A. Tyndall, Gautam Adhikary, Richard L. Eckert, Jeffrey W. Keillor
Summary: The multifunctional protein tissue transglutaminase (TG2) plays a key role in protein crosslinking and intracellular G-protein functions, with implications in diseases and cancer stem cell survival. A recent study focused on developing covalent inhibitors to selectively target the enzyme active site of TG2, showing promising results in enhancing efficiency and affinity for TG2. Molecular modelling was used to understand the binding mode of the inhibitors, with the most efficient ones demonstrating isozyme selectivity, blocking GTP binding, and improved pharmacokinetic properties.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Leon C. D. Smyth, Helen C. Murray, Madison Hill, Eve van Leeuwen, Blake Highet, Nicholas J. Magon, Mahyar Osanlouy, Sophie N. Mathiesen, Bruce Mockett, Malvindar K. Singh-Bains, Vanessa K. Morris, Andrew N. Clarkson, Maurice A. Curtis, Wickliffe C. Abraham, Stephanie M. Hughes, Richard L. M. Faull, Anthony J. Kettle, Mike Dragunow, Mark B. Hampton
Summary: This study found that neutrophil accumulation in Alzheimer's disease is associated with cognitive impairment. The oxidant-generating enzyme myeloperoxidase (MPO) expressed in neutrophils could be a potential therapeutic target for AD. Vascular changes may drive neutrophil adhesion and NETosis.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Eveline van Leeuwen, Mark B. Hampton, Leon C. D. Smyth
Summary: Inflammation is a common feature in neurological diseases. This study demonstrates that a compound called hypothiocyanous acid can damage brain endothelial cells and result in the loss of barrier function, which may be a mechanism involved in neutrophil transmigration and neuroinflammation.
Article
Biochemistry & Molecular Biology
Heather L. Shearer, Paul E. Pace, James C. Paton, Mark B. Hampton, Nina Dickerhof
Summary: This study reports the discovery of a previously unknown flavoprotein disulfide reductase with HOSCN reductase activity in HOSCN-tolerant Streptococcus pneumoniae, and demonstrates the role of this protein in combination with GSH utilization in protecting the bacteria from HOSCN.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
A. Swaminathan, G. M. Borichevsky, T. S. Edwards, E. Hirschfeld, T. C. Mules, C. M. Frampton, A. S. Day, M. B. Hampton, A. J. Kettle, R. B. Gearry
Summary: This study investigated the use of faecal myeloperoxidase (fMPO) as a biomarker for the activity of inflammatory bowel disease (IBD). The results showed that fMPO was significantly correlated with endoscopic activity and could accurately predict the severity and complexity of the disease.
JOURNAL OF CROHNS & COLITIS
(2022)
Review
Immunology
Mark B. Hampton, Nina Dickerhof
Summary: The neutrophil phagosome poses a challenging environment for bacteria, but our understanding of the complex biochemistry within it is incomplete. Heterogeneity among phagosomes suggests that investigating the conditions that allow bacteria to survive could lead to new therapeutic strategies. Monitoring or recovering bacteria from phagosomes and unbiased screening for essential bacterial genes are important for gaining insights into their survival mechanisms inside neutrophil phagosomes.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Chemistry, Physical
Jiazhen Yin, Raahul Sharma, Joel D. A. Tyndall, Natasha L. Grimsey, Andrea J. Vernall
Summary: GPCR ligand prodrugs that can be released on demand have important applications in studying the consequences of GPCR activation or blockade. The development and characterization of a cannabinoid type 2 receptor agonist prodrug based on a photo caging moiety is described here. The prodrug showed rapid photolysis and good stability, but had significantly decreased binding affinity to the human cannabinoid type 2 receptor compared to the active parent ligand.
Article
Biochemistry & Molecular Biology
Heather L. Shearer, Vu V. Loi, Paul Weiland, Gert Bange, Florian Altegoer, Mark B. Hampton, Haike Antelmann, Nina Dickerhof
Summary: A study reveals that Staphylococcus aureus has developed a defense mechanism against the antimicrobial oxidant hypothiocyanous acid (HOSCN) in order to cause infections in humans. The enzyme MerA acts as a HOSCN reductase, protecting the bacteria from oxidative stress. Understanding the structure and function of MerA may lead to new strategies for treating S. aureus infections.
MOLECULAR MICROBIOLOGY
(2023)
Article
Hematology
Halima Siddiqui, Nikita Deo, Malcolm T. Rutledge, Michael J. A. Williams, Gregory M. I. Redpath, Sally P. A. Mccormick
Summary: This study identifies multiple plasminogen receptors involved in the endocytosis of Lp(a), which enhance surface binding and stimulate macropinocytosis of Lp(a). While the findings were obtained in cell culture models with limitations, they could have clinical relevance due to the availability of drugs that inhibit macropinocytosis for cancer therapy and antidepressant compounds.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Microbiology
Heather L. Shearer, Paul E. Pace, Leah M. Smith, Peter C. Fineran, Allison J. Matthews, Andrew Camilli, Nina Dickerhof, Mark B. Hampton
Summary: By using saturation transposon mutagenesis and deep sequencing, this study identified 37 genes associated with hypothiocyanous acid (HOSCN) tolerance in Streptococcus pneumoniae. These genes are involved in metabolism, membrane transport, DNA repair, and oxidant detoxification. Validation experiments showed that most of the single-gene deletion mutants exhibited increased sensitivity to HOSCN, and some mutants showed enhanced activity of antioxidant defense systems. The double deletion of glutathione reductase and sodA significantly sensitized the bacteria. The HOSCN defense systems identified in this study may serve as viable targets for novel therapeutics against S. pneumoniae.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)