Article
Infectious Diseases
Meng-Rui Lee, Yen-Lin Chen, Chang-Wei Wu, Lun-Che Chen, Lih-Yu Chang, Jung-Yueh Chen, Yu-Tsung Huang, Jann-Yuan Wang, Jin-Yuan Shih, Chong-Jen Yu
Summary: This study found that single nucleotide polymorphisms (SNPs) in Toll-like receptor 1 (TLR1), Toll-like receptor 2 (TLR2), and matrix metalloproteinase 8 (MMP8) were associated with the risk of tuberculosis (TB) infection and disease. Haplotypes and a polygenic risk score (PRS) could be used to predict TB disease status.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(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
Biochemistry & Molecular Biology
Yang Liu, Fei Wang, Zhe Li, Yanling Mu, Voon Wee Yong, Mengzhou Xue
Summary: This study found that chlorogenic acid (CGA) can provide neuroprotection in intracerebral hemorrhage (ICH) by inhibiting the expression of EMMPRIN and MMP-2/9, alleviating neuroinflammation, blood-brain barrier disruption, cell death, and brain injury.
Review
Biochemistry & Molecular Biology
Lokender Kumar, Monish Bisen, Azhar Khan, Pradeep Kumar, Sanjay Kumar Singh Patel
Summary: This review discusses the role of MMPs in skeletal muscle function, muscle injury and repair, as well as the potential applications of MMPs in the treatment of musculoskeletal disorders.
Letter
Oncology
Patrick Tassone, Carla Caruso, Meghan White, Harim Tavares Dos Santos, Tabitha Galloway, Laura Dooley, Robert Zitsch, J. Lester Layfield, Olga Baker
Summary: This study investigated the role of perineural fibroblasts in oral cavity squamous cell carcinoma (OCSCC) with perineural invasion (PNI) and their expression of matrix metalloproteinase-2 (MMP-2). The results showed that fibroblasts expressed MMP-2 in the microenvironment of PNI, suggesting that MMP-2 may be involved in the invasion process of OCSCC via PNI.
Article
Biochemistry & Molecular Biology
Eduardo P. Amaral, Caian L. Vinhaes, Deivide Oliveira-de-Souza, Betania Nogueira, Kevan M. Akrami, Bruno B. Andrade
Summary: Persistent and exacerbated oxidative stress responses in chronic tuberculosis are associated with severe pathology. Inhibition of this stress response by improving host antioxidant status may be a strategy to reduce tissue damage. Future research should focus on host-directed therapy to prevent severe immunopathology in TB.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Biochemistry & Molecular Biology
Ya-Tang Chiang, Yu-Bai Xiao, Shan-hui Hsu, Shu-Wei Chang, Chia-Ching Chou
Summary: Tannic acid (TA) has antibacterial, antioxidant, and anti-inflammatory properties and acts as an adhesive, hemostatic, and crosslinking agent in hydrogels. TA has been reported to inhibit MMP-2/- 9 activities, thereby improving tissue remodeling and wound healing. In this study, atomistic modeling was used to explore the mechanisms and structures of TA binding with MMP-2 and MMP-9, revealing the specific binding regions and molecular interactions involved. Understanding the binding mechanism and dynamics of TA with these MMPs provides crucial knowledge on the effects of TA on MMPs.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Medicine, General & Internal
Qi Ning, Ye-Hua Gan, Rui-Rui Shi, Juan-Hong Meng
Summary: The study found that HDAC4 has an inhibitory effect on IL-1 beta-induced chondrocyte extracellular matrix degradation, which is partially regulated through the WNT3A/beta-catenin signaling pathway.
CHINESE MEDICAL JOURNAL
(2021)
Review
Medicine, Research & Experimental
Liang Shan, Fengling Wang, Dandan Zhai, Xiangyun Meng, Jianjun Liu, Xiongwen Lv
Summary: Liver fibrosis is a consequence of chronic liver injuries, characterized by the imbalance of extracellular matrix production and degradation. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are crucial in collagen synthesis and lysis. This article reviews experimental studies on liver fibrosis based on MMPs/TIMPs and highlights the potential of targeting this interaction as a therapeutic strategy for hepatic fibrosis. The article also summarizes drugs, including natural products, that have been found to reduce liver fibrosis by altering the ratio of MMPs/TIMPs.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, General & Internal
Ionut Luchian, Mihaela Moscalu, Ancuta Goriuc, Ludovica Nucci, Monica Tatarciuc, Ioana Martu, Mihai Covasa
Summary: Periodontitis results in destructive effects on periodontium, with increased levels of MMP-9. Periodontal treatment alone or combined with orthodontic treatment can improve clinical parameters and lower MMP-9 levels. The degree of malocclusion affects the treatment's impact on MMP-9 levels.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Chemistry, Medicinal
Sanjib Das, Sk Abdul Amin, Tarun Jha
Summary: Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) play significant roles in solid tumor invasion, metastasis, and angiogenesis, while their role in hematological malignancies is less understood. Recent studies have shown correlations between gelatinases and hematological malignancies, leading to the development of potential inhibitors for these conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, General & Internal
Zhongyang Zhao, Minghui Liang, Huan He, Xuemei Wang, Chengfang Zhu, Lan Li, Bin Liu, Rongrong Zong, Qifang Jin, Huping Wu, Wei Li, Zhirong Lin
Summary: The study revealed that allergic conjunctivitis affects corneal microstructures and biomechanical stability in rabbits, but can be maintained with topical anti-inflammatory treatment.
FRONTIERS IN MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Shinji Takai, Denan Jin
Summary: Chymase-activated MMP-9 is closely related to the pathogenesis of various diseases, especially inflammation-related diseases. Upregulated chymase and MMP-9 have been observed in tissues from patients and animal models of these diseases. Chymase inhibitors attenuate MMP-9 formation and reduce inflammatory cell numbers, thereby ameliorating the development and progression of these disorders.
Review
Chemistry, Physical
Lavanya Anumula, Sindhu Ramesh, Venkata Suneel Kumar Kolaparthi, Richard Kirubakaran, Mohmed Isaqali Karobari, Suraj Arora, Ahmed A. Saleh, Omir Aldowah, Pietro Messina, Giuseppe Alessandro Scardina
Summary: The present study aimed to systematically review the effects of natural cross-linkers on immediate and long-term tensile bond strength and concluded that Proanthocyanidin is the most efficient natural cross-linker to date, preserving bond strength even after ageing.
Article
Cardiac & Cardiovascular Systems
Xin-sheng Deng, Xianzhong Meng, David Fullerton, Matthew Stone, James Jaggers
Summary: This study demonstrates that complement induces profibrogenic activities in aortic valve interstitial cells through the activation of ERK1/2-mediated Runx-2 signaling pathways, suggesting a potential therapeutic target to limit the progression of calcific aortic valve disease.
ANNALS OF THORACIC SURGERY
(2021)
Article
Ophthalmology
Soumyava Basu, Narsing Rao, Paul Elkington
Summary: This review critically examines various animal models of ocular TB, providing novel insights into the pathogenesis of the disease that have direct implications for diagnosis and treatment. The future directions of experimental approaches to understanding the pathogenesis of ocular TB are also discussed.
OCULAR IMMUNOLOGY AND INFLAMMATION
(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
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
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
Medicine, Research & Experimental
Michaela T. Reichmann, Liku B. Tezera, Andres F. Vallejo, Milica Vukmirovic, Rui Xiao, James Reynolds, Sanjay Jogai, Susan Wilson, Ben Marshall, Mark G. Jones, Alasdair Leslie, Jeanine M. D'Armiento, Naftali Kaminski, Marta E. Polak, Paul Elkington
Summary: The research found many shared pathological mechanisms between tuberculosis and sarcoidosis, and also revealed tuberculosis results from a dysregulated inflammatory immune response. By comparing human cell culture models, potential therapeutic targets were identified.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Engineering, Biomedical
Alasdair Munro, Jacqui Prieto, Emmanouil Mentzakis, Mohammed Dibas, Nitin Mahobia, Peter Baker, Sarah Herbert, Trevor Smith, Matthew Hine, Joann Hall, Angie McClarren, Mike Davidson, Julie Brooks, Jane Fisher, David Griffiths, Hywel Morgan, Corrado Giulietti, Saul N. Faust, Paul Elkington
Summary: The powered air-purifying respirator (PeRSo) was preferred by healthcare workers over droplet precautions, leading to better comfort, patient response, overall experience, and subjective feeling of safety. Economic simulation exercises revealed cost savings with the adoption of PeRSo in ICU settings.
FRONTIERS IN MEDICAL TECHNOLOGY
(2021)
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)
Article
Medicine, Research & Experimental
Paul Ogongo, Liku B. Tezera, Amanda Ardain, Shepherd Nhamoyebonde, Duran Ramsuran, Alveera Singh, Abigail Ng'oepe, Farina Karim, Taryn Naidoo, Khadija Khan, Kaylesh J. Dullabh, Michael Fehlings, Boon Heng Lee, Alessandra Nardin, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Samuel M. Behar, Adrie J. C. Steyn, Rajhmun Madansein, Henrik N. Kloverpris, Paul T. Elkington, Alasdair Leslie
Summary: The study identified distinct CD4(+) and CD8(+) tissue-resident memory T cells (Trms) enriched for IL-17-producing cells in lung tissue of individuals with active or previous TB. M. tuberculosis-specific T cells producing TNF-alpha, IL-2, and IL-17 were highly expanded in the lung compared to blood samples, and the frequency of IL-17-producing lung T cells inversely correlated with plasma IL-1 beta levels. Additionally, adding exogenous IL-17 or IL-2 enhanced immune control of M. tuberculosis in a human granuloma model, suggesting a potential role for IL-17-producing Trm-like cells in immune control of M. tuberculosis in the human lung.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Engineering, Biomedical
Paul T. Elkington, Alexander S. Dickinson, Mark N. Mavrogordato, Daniel C. Spencer, Richard J. Gillams, Antonio De Grazia, Sebastian Rosini, Diana J. Garay-Baquero, Laura E. Diment, Nitin Mahobia, Alexandra Mant, Tom Baynham, Hywel Morgan
Summary: This study addresses the challenges of providing adequate PPE for healthcare workers during the global pandemic, with a focus on developing a simple powered air purifying respirator called PeRSo. The prototype successfully removes microbes, avoids excessive CO2 build-up, and is preferred by healthcare workers over standard face masks, improving comfort and efficiency in healthcare settings. Rapidly scaling production of such respirators could protect healthcare workers from infection and enhance healthcare delivery during the COVID-19 pandemic.
FRONTIERS IN MEDICAL TECHNOLOGY
(2021)