Review
Biochemistry & Molecular Biology
Anastasiia Diatlova, Natalia Linkova, Anastasia Lavrova, Yulia Zinchenko, Dmitrii Medvedev, Alexandr Krasichkov, Victoria Polyakova, Piotr Yablonskiy
Summary: Tuberculosis remains a major public health problem, and the diagnosis of different stages and early identification of infected individuals have not been resolved. Current tests cannot predict active TB development in individuals with latent infection. This review analyzes the interaction of M. tuberculosis with immune cells and identifies molecular markers for different stages of TB.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Neha Dubey, Mehak Zahoor Khan, Suresh Kumar, Aditya Sharma, Lahari Das, Asani Bhaduri, Yogendra Singh, Vinay Kumar Nandicoori
Summary: PPiA not only assists in the survival of Mtb but also promotes disease progression by affecting host cell status through interaction with host-related factors.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Arpana Verma, Maninder Kaur, Princy Luthra, Lakshyaveer Singh, Divya Aggarwal, Indu Verma, Bishan D. D. Radotra, Sanjay Kumar Bhadada, Sadhna Sharma
Summary: Diabetes is a significant risk factor for latent tuberculosis activation and worsens tuberculosis treatment outcomes. The study focuses on understanding the interaction between M. tuberculosis and its host during latent tuberculosis infection under hyperglycemic conditions or diabetes. An animal model was used to study the relationship, and various host factors such as cytokines and MMPs were analyzed. The results showed that diabetes worsens the containment of mycobacterial infection and affects granuloma formation.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Immunology
Xuan Ying Poh, Fei Kean Loh, Jon S. Friedland, Catherine W. M. Ong
Summary: Tuberculosis (TB) is a major infectious disease worldwide, with central nervous system tuberculosis (CNS-TB) being the most severe form. Neutrophils play a crucial role in CNS-TB by carrying out antimicrobial functions and mediating inflammation and tissue destruction.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Helena Laronha, Ines Carpinteiro, Jaime Portugal, Ana Azul, Mario Polido, Krasimira T. Petrova, Madalena Salema-Oom, Isabel Barahona, Jorge Caldeira
Summary: A new class of MMP inhibitors has been discovered, which can be co-polymerized with other vinyl compounds in commercial dental resins, limiting release and potential toxicity, and increasing safety. These inhibitors show unique properties towards various MMPs and did not significantly decrease cell viability at high concentrations.
Article
Hematology
Manuel Navarro-Oviedo, Juan Marta-Enguita, Carmen Roncal, Jose A. Rodriguez, Beatriz Zandio, Ramon Lecumberri, Jose Hermida, Julen Oyarzabal, Antonio Pineda-Lucena, Jose A. Paramo, Roberto Munoz, Josune Orbe
Summary: This study evaluated the effects of CM-352 in an experimental ICH model associated with oral anticoagulants and compared it with clinically used PCC. The results showed that CM-352 can reduce hemorrhage volume and improve functional outcome. Additionally, CM-352 can also reduce neutrophil infiltration by inhibiting MMP-10 and rivaroxaban-related fibrinolytic effects.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Matteo Giovarelli, Francesca Arnaboldi, Silvia Zecchini, Laura Brigida Cornaghi, Ambra Nava, Michele Sommariva, Emilio Giuseppe Ignazio Clementi, Nicoletta Gagliano
Summary: This study provides a comprehensive histological and molecular characterization of muscle fibrosis in Duchenne muscular dystrophy (DMD), showing that fibrosis mainly affects the diaphragm and quadriceps with higher collagen cross-linking and inhibition of MMPs. These findings may lead to new targeted therapeutic interventions for DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Aditya N. Bade, JoEllyn M. McMillan, Yutong Liu, Benson J. Edagwa, Howard E. Gendelman
Summary: Research indicates that Dolutegravir inhibits matrix metalloproteinases activities that could affect fetal neurodevelopment, with studies in pregnant mice showing that DTG reaches the fetal central nervous system and leads to neuroinflammation and neuronal impairment.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Min-Ha Choi, Jinhyun Kim, Jeong Hyun Ha, Ji-Ung Park
Summary: PHA-665752 can suppress keloid fibroblast activity by inhibiting the c-Met-related tyrosine kinase pathway. In vivo experiments showed that PHA-665752-treated mice had lower nodule volumes and weights, accompanied by less inflammatory cell infiltration and collagen deposition.
SCIENTIFIC REPORTS
(2021)
Article
Materials Science, Multidisciplinary
Richard J. R. Kelwick, Alexander J. Webb, Yizhou Wang, Amelie Heliot, Fiona Allan, Aidan M. Emery, Michael R. Templeton, Paul S. Freemont
Summary: The ALPHA beads, containing a library of low-cost, biodegradable protease biosensors utilizing PhaC-reporter fusion proteins, can detect specific proteases in various samples and have the potential for use in resource-limited settings.
Article
Cardiac & Cardiovascular Systems
Anca Remes, Rawa Arif, Maximilian Franz, Andreas Jungmann, Marcin Zaradzki, Thomas Puehler, Markus B. Heckmann, Norbert Frey, Matthias Karck, Klaus Kallenbach, Markus Hecker, Oliver J. Mueller, Andreas H. Wagner
Summary: This study aimed to establish a novel AAV-based strategy for long-term expression of AP-1 neutralizing RNA hairpin in the aorta to prevent aortic elastolysis in a murine model of Marfan syndrome. The results showed that this approach effectively reduced MMP expression and activity, ROS formation, and inflammation in the aortic tissue.
CARDIOVASCULAR RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Milosz Caban, Katarzyna Owczarek, Urszula Lewandowska
Summary: Eye diseases are linked to visual impairment and reduced quality of life. Current treatments for these diseases are not satisfactory, highlighting the need for new therapeutic approaches. Matrix metalloproteinases and tissue inhibitors of metalloproteinases play crucial roles in eye diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Cansu Kaya, Jelena Konstantinovic, Andreas M. Kany, Anastasia Andreas, Jan S. Kramer, Steffen Brunst, Lilia Weizel, Marco J. Rotter, Denia Frank, Samir Yahiaoui, Rolf Mueller, Rolf W. Hartmann, Joerg Haupenthal, Ewgenij Proschak, Thomas A. Wichelhaus, Anna K. H. Hirsch
Summary: Drug-resistant pathogens pose a global challenge to public health, and metallo-beta-lactamases (MBLs) are enzymes that catalyze the hydrolysis of beta-lactam drugs, including carbapenems. We have identified a series of inhibitors that effectively inhibit the activity of B1 MBLs, restoring the effectiveness of current beta-lactam antibiotics. In experiments, one of the inhibitors significantly reduced the minimum inhibitory concentration of resistant Escherichia coli strains, and the combination with imipenem also increased the survival rate of infected larvae in a model.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Christian Behm, Michael Nemec, Fabian Weissinger, Marco Aoqi Rausch, Oleh Andrukhov, Erwin Jonke
Summary: The systematic review revealed that orthodontic forces induce increased expression levels of MMPs and TIMPs in the PDL during orthodontic tooth movement. However, the exact effect may vary depending on intervention and sample parameters as well as subject characteristics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Rohit Siddhartha, Minal Garg
Summary: MMPs are a group of enzymes that play a crucial role in degrading proteins in the extracellular matrix and regulating cell signaling. Dysregulation of MMPs can lead to serious pathological conditions such as inflammation, uncontrolled cell growth, and cancer metastasis. Understanding the functions of MMPs has potential implications for cancer diagnosis, prognosis, and therapy.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Chemistry, Analytical
Alice H. Iles, Peijun J. W. He, Ioannis N. Katis, Panagiotis P. Galanis, Anto J. U. K. John, Paul Elkington, Robert W. Eason, Collin L. Sones
Summary: Inflammatory markers CRP and PCT are useful in improving triage speed and preventing inappropriate antibiotic use. A novel multiplexed LFD can rapidly and semi-quantitatively detect CRP and PCT, showing potential for rapid treatment of patients with suspected pneumonia.
Review
Respiratory System
Tommaso Morelli, Kohei Fujita, Gil Redelman-Sidi, Paul T. Elkington
Summary: Immune checkpoint inhibitors (ICIs) have greatly impacted cancer treatment, but immune-related adverse events (irAEs) and infections caused by immunosuppression are common issues. However, some infections can be triggered by ICIs without immunosuppressive treatment, characterized by dysregulated immune responses. A new framework is needed to consider such infections in the context of cancer immunotherapy.
Review
Biochemistry & Molecular Biology
Paul Elkington, Marta E. Polak, Michaela T. Reichmann, Alasdair Leslie
Summary: Mycobacterium tuberculosis is the main pathogen causing tuberculosis and poses a serious threat to human health. Understanding its pathogenic mechanisms is crucial for effectively combating this pathogen. Recent studies have found that extracellular matrix (ECM) remodeling plays an important role in the development of the disease.
TRENDS IN MOLECULAR MEDICINE
(2022)
Article
Medicine, Research & Experimental
Alvaro A. Ordonez, Matthew F. L. Parker, Robert J. Miller, Donika Plyku, Camilo A. Ruiz-Bedoya, Elizabeth W. Tucker, Justin M. Luu, Dustin A. Dikeman, Wojciech G. Lesniak, Daniel P. Holt, Robert F. Dannals, Lloyd S. Miller, Steven P. Rowe, David M. Wilson, Sanjay K. Jain
Summary: This study successfully used C-11-PABA PET imaging to accurately detect and monitor pyogenic bacterial infections in multiple clinically relevant animal models. It also demonstrated the potential clinical translation of C-11-PABA for detecting and localizing a broad range of bacteria.
Article
Microbiology
Jianhao Lai, Swati Shah, Rekeya Knight, Neysha Martinez-Orengo, Reema Patel, Amelia Mitchell, Zeping Wang, Falguni Basuli, Alvaro A. Ordonez, Sanjay K. Jain, Dima A. Hammoud
Summary: The diagnosis of fungal infections, especially with Aspergillus fumigatus, is still challenging. The study found low uptake of the newly described Enterobacterales imaging ligand FDS by A. fumigatus, suggesting that FDS is not a suitable imaging agent for Aspergillus.
Article
Oncology
Kohei Fujita, Paul Elkington, Gil Redelman-Sidi, Osamu Kanai, Yuki Yamamoto, Takuma Imakita, Misato Okamura, Koichi Nakatani, Tadashi Mio
Summary: This study evaluated the conversion rate of interferon-gamma release assay (IGRA) and the incidence of active tuberculosis during immunotherapy, finding that some patients developed IGRA conversion and active tuberculosis during ICI therapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Review
Respiratory System
Mohamed Ahmed, Liku B. Tezera, Paul T. Elkington, Alasdair J. Leslie
Summary: Immune checkpoints play a crucial role in regulating T-cell activation and can limit anti-tumour responses. However, boosting T-cell immunity by blocking the PD-1/PD-L1 axis can trigger reactivation of latent tuberculosis. Inhibitory receptors are important for maintaining immune function and preventing excessive tissue damage.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Immunology
N. F. Walker, F. Karim, M. Y. S. Moosa, S. Moodley, M. Mazibuko, K. Khan, T. R. Sterling, Y. F. van der Heijden, A. D. Grant, P. T. Elkington, A. Pym, A. Leslie
Summary: Current methods for tuberculosis treatment monitoring are not optimal. This study evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations as potential biomarkers for tuberculosis treatment monitoring. The results showed that plasma concentrations of MMP-1, MMP-8, and MMP-10 decreased significantly during treatment, while plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive participants, both before and after 6 months of treatment. Therefore, plasma MMP-8 has the potential to enhance tuberculosis treatment monitoring and screen for culture positivity.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Biology
Alvaro A. Ordonez, C. Korin Bullen, Andres F. Villabona-Rueda, Elizabeth A. Thompson, Mitchell L. Turner, Vanessa F. Merino, Yu Yan, John Kim, Stephanie L. Davis, Oliver Komm, Jonathan D. Powell, Franco R. D'Alessio, Robert H. Yolken, Sanjay K. Jain, Lorraine Jones-Brando
Summary: This study evaluated the antiviral activity of sulforaphane (SFN) against SARS-CoV-2 and found that SFN can inhibit the replication of multiple strains of SARS-CoV-2 and seasonal coronaviruses. Prophylactic SFN treatment can reduce viral load, lung injury, and immune cell activation in infected mice.
COMMUNICATIONS BIOLOGY
(2022)
Article
Respiratory System
Maria Victoria Humbert, Cosma Mirella Spalluto, Joseph Bell, Cornelia Blume, Franco Conforti, Elizabeth R. Davies, Lareb S. N. Dean, Paul Elkington, Hans Michael Haitchi, Claire Jackson, Mark G. Jones, Matthew Loxham, Jane S. Lucas, Hywel Morgan, Marta Polak, Karl J. Staples, Emily J. Swindle, Liku Tezera, Alastair Watson, Tom M. A. Wilkinson
Summary: Respiratory diseases are a significant burden to healthcare systems globally, and the differences in mouse models hinder the translation of research findings to the clinic. Therefore, it is crucial to develop models that accurately recreate the complexity of the human lung. Advances in micro-engineering and tissue engineering have enabled the development of more sophisticated models aiming to bridge the gap between native lungs and in vitro replicates.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Infectious Diseases
Ximena Gonzalo, Magdalena K. Bielecka, Liku Tezera, Paul Elkington, Francis Drobniewski
Summary: In this study, a novel physiological 3-D bioelectrospray model of tuberculosis granuloma was used to evaluate the activity of different drugs. The results showed that clofazimine was the most effective drug, while carbapenems and nitazoxanide had less activity against Mycobacterium tuberculosis.
Article
Biology
Mohamed Ahmed, Jared Mackenzie, Liku Tezera, Robert Krause, Barry Truebody, Diana Garay-Baquero, Andres Vallejo, Katya Govender, John Adamson, Hayden Fisher, Jonathan W. Essex, Salah Mansour, Paul Elkington, Adrie J. C. Steyn, Alasdair Leslie
Summary: Studies have shown that Interferon-gamma (IFN-gamma) has a direct effect on the oxygen consumption rate and respiration of Mycobacterium tuberculosis (Mtb), different from other cytokines. Mass spectrometry and molecular modeling studies have revealed that IFN-gamma interacts with mycobacterial membrane protein large 10 (MmpL10). Furthermore, IFN-gamma promotes Mtb growth and eliminates drug-resistant strains.
COMMUNICATIONS BIOLOGY
(2022)
Article
Microbiology
Stefanie Krug, Pankaj Prasad, Shiqi Xiao, Shichun Lun, Camilo A. A. Ruiz-Bedoya, Mariah Klunk, Alvaro A. A. Ordonez, Sanjay K. K. Jain, Geetha Srikrishna, Igor Kramnik, William R. R. Bishai
Summary: Despite advances in TB drug development, multidrug resistance remains a major challenge for global TB control. Host-directed therapies, such as inhibition of the integrated stress response (ISR), have the potential to improve the efficacy of tuberculosis antibiotics. In this study, we evaluated the impact of ISR inhibition on bacterial clearance, relapse, and lung pathology in a mouse model of TB. Our findings suggest that adjunctive ISR inhibition can accelerate bacterial clearance, reduce relapse rates, and improve lung health.
Article
Medicine, Research & Experimental
Qing Hao Miow, Andres F. Vallejo, Yu Wang, Jia Mei Hong, Chen Bai, Felicia S. W. Teo, Alvin D. Y. Wang, Hong Rong Loh, Tuan Zea Tan, Ying Ding, Hoi Wah She, Suay Hong Gan, Nicholas Paton, Josephine Lum, Alicia Tay, Cynthia B. E. Chee, Paul A. Tambyah, Marta E. Polak, Yee Tang Wang, Amit Singhal, Paul T. Elkington, Jon S. Friedland, Catherine W. M. Ong
Summary: The study demonstrated the pathological inhibition effect of doxycycline on matrix metalloproteinases (MMPs) in patients with pulmonary tuberculosis, and it could accelerate the restoration of gene expression. Doxycycline not only reduced the levels of MMPs in sputum of tuberculosis patients, but also inhibited the destruction of collagen and elastin, showing significant differences compared to placebo.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
