Article
Environmental Sciences
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi, Sang Rul Park, Seungheon Lee, Gi-Young Kim
Summary: Low concentrations of BPA induce inflammation by activating the NF-kappa B signaling pathway and increasing the release of proinflammatory mediators. Molecular modeling suggests that BPA binds to the TLR4/MD2 complex to initiate downstream molecules and elicit an immune response.
ENVIRONMENTAL POLLUTION
(2021)
Article
Pharmacology & Pharmacy
Thura Tun Oo, Natticha Sumneang, Benjamin Ongnok, Busarin Arunsak, Titikorn Chunchai, Sasiwan Kerdphoo, Nattayaporn Apaijai, Wasana Pratchayasakul, Guang Liang, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: The study demonstrated that the MD-2 inhibitor L6H21 and metformin can attenuate metabolic disturbances and restore cognitive function in a model of prediabetes induced by high-fat diet.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Immunology
Wei Zhang, Eun-Koung An, Juyoung Hwang, Jun-O Jin
Summary: The study found that LPS can directly stimulate pDCs via the TLR4/MD2 pathway and promote the activation of pDCs and cDCs. cDCs may contribute to the enhancement of IFN-alpha production in pDCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, Research & Experimental
Xiao Li, Xinyuan Sun, Xuemin Guo, Xueren Li, Shouchun Peng, Xin Mu
Summary: Nucleic acid-mediated interferon signaling plays a pivotal role in defense against microorganisms, especially during viral infection. This article discusses the receptors involved in sensing nucleic acid molecules, their structures and functions, and the importance of their proper functioning in cell homeostasis and response to pathogen invasion. It also explores the impact of manipulating these receptors on defense mechanisms and presents the discovery of chemicals that can modulate their signaling activities.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biotechnology & Applied Microbiology
Danieli F. Buccini, Beatriz C. Roriz, Julia M. Rodrigues, Octavio L. Franco
Summary: Antimicrobial peptides are important molecules in the organism's defense system. They can modulate the immune system and recognize molecules present in pathogens. Overstimulation of TLR4 can lead to uncontrolled inflammatory responses, which can be counteracted by antimicrobial peptides.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Medicinal
Yongsheng Zhang, Xinjie Liang, Xuefei Bao, Wei Xiao, Guoliang Chen
Summary: This review discusses TLR4 inhibitors that can bind directly to TLR4 or the TLR4/MD2 complex, as well as compounds that can downregulate the expression of TLR4. The involvement of specific residues in the binding of antagonistic ligands to the TLR4/MD2 complex provides useful information for structure-based TLR4 inhibitor design.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Irina Stefanelli, Angela Corona, Carmen Cerchia, Emilia Cassese, Salvatore Improta, Elisa Costanzi, Sveva Pelliccia, Stefano Morasso, Francesca Esposito, Annalaura Paulis, Sante Scognamiglio, Francesco Saverio Di Leva, Paola Storici, Margherita Brindisi, Enzo Tramontano, Rolando Cannalire, Vincenzo Summa
Summary: Despite the availability of vaccines, monoclonal antibodies, and restrictions, there is a strong demand for new antiviral drugs that are both effective and safe against COVID-19. This study describes the design, synthesis, and biological activity of peptidomimetic covalent reversible inhibitors targeting the viral 3-chymotrypsin-like protease (3CLpro) which is essential for viral replication. These inhibitors showed potent activity against multiple coronaviruses, including SARS-CoV-2, MERS-CoV, and HCoV 229. The results suggest that these inhibitors have the potential to be developed as broad-spectrum antiviral drugs against future coronavirus pandemics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mehr-un-Nisa, Munawar A. Munawar, David Rankin, Victor J. Hruby, Frank Porreca, Yeon Sun Lee
Summary: A new series of enkephalin-like tetrapeptide analogs modified with a DPP moiety were synthesized and evaluated for their binding affinities at opioid receptors and monoamine transporters for potential treatment of chronic pain. The ligands exhibited high opioid receptor affinity with DOR selectivity and low monoamine transporter binding affinities, with one ligand showing particularly high affinity at the KOR.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biology
Jorge Gonzalez-Bacerio, Irina Arocha, Mirtha Elisa Aguado, Yanira Mendez, Sabrina Marsiccobetre, Maikel Izquierdo, Daniel G. Rivera, Katherine Figarella, Nestor L. Uzcategui
Summary: The research discovered that the peptidomimetic KBE009 inhibits TcLAP and proliferative activity of T. cruzi in vitro with selectivity for the parasite over human cells. Docking simulations using crystal structures showed KBE009 had better geometrical shape and stability in TcLAP compared to its human orthologous hLAP3, suggesting potential as a starting compound for drug design.
Article
Pharmacology & Pharmacy
Natticha Sumneang, Nattayaporn Apaijai, Siriporn C. Chattipakorn, Nipon Chattipakorn
Summary: MD2 plays a crucial role in cardiac inflammation and dysfunction, and its inhibitors have potential benefits for cardiac diseases such as obesity and heart failure.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Sandra Santos-Sierra
Summary: Inflammatory arthritis is a group of diseases caused by dysregulated immune system activity, and various medications are used to control the excessive immune response. However, drug resistances, flare-reactions, and adverse effects to current therapies are common in affected patients.
Article
Hematology
Mina Noura, Ken Morita, Hiroki Kiyose, Yukiko Okuno, Hidemasa Matsuo, Asami Koyama, Yoko Nishinaka-Arai, Yasuhiko Kamikubo, Souichi Adachi
Summary: Differentiation therapy, specifically using albendazole to stimulate a differentiation axis, shows promise as a novel treatment for non-APL acute myeloid leukaemia (AML), with potential efficacy both in vitro and in vivo.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Claudine Nicole Herlan, Katharina Sommer, Patrick Weis, Martin Nieger, Stefan Brase
Summary: Peptoids exhibit broad structural diversity compared to peptides, with certain side chains influencing their backbone conformations to form different secondary structures. The copper-catalysed reaction has enabled the creation of innovative tube-like tricyclic peptoids, allowing for size tuning and light-triggered conformational changes.
Review
Cell Biology
Xiaoyang Liu, Zongke Zhou, Wei-Nan Zeng, Qin Zeng, Xingdong Zhang
Summary: Osteoimmunology involves crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) play a crucial role in bone remodeling by directly impacting MSC osteogenic differentiation. Understanding TLRs' role has significant implications for advancing bone regeneration and repair strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Chemistry, Physical
Patrycja Ledwon, Anna Maria Papini, Paolo Rovero, Rafal Latajka
Summary: Collagen fibres degradation involves a variety of enzymes, with fibrillar collagens like type I, II, and III being responsible for tissue structure and skin elasticity. Understanding the enzymes involved in collagen degradation, especially those degrading fibrillar collagen, can be valuable for future research and applications.
Article
Cell Biology
Bonnie Williams, Florence Lees, Helen Tsangari, Mark R. Hutchinson, Egon Perilli, Tania N. Crotti
Summary: This study aimed to compare macroscopic and microscopic changes in the paws, along with central nervous system activation between a mild and moderate CAIA model. The moderate CAIA dose induced significantly greater local paw inflammation, inflammatory cell infiltration, and glial reactivity within the brain compared to the mild CAIA model. These findings support the use of a moderate CAIA model to induce more consistent histopathological features without excessive joint destruction.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2021)
Article
Neurosciences
Juliana Esma Bajic, Gordon Stanley Howarth, Suzanne Mashtoub, Alexandra Louise Whittaker, Larisa Bobrovskaya, Mark Rowland Hutchinson
Summary: This study investigates the effects of different analgesics on central glial reactivity and proinflammatory changes in rats with chemotherapy-induced gut toxicity (CIGT). While carprofen and buprenorphine showed beneficial effects in ameliorating neuroimmune responses, tramadol presented complications and may not be optimal in managing pain associated with CIGT. The findings suggest potential mechanisms contributing to cancer symptom clusters and have implications for optimal pain management in this setting.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Agriculture, Dairy & Animal Science
Laura Marsh, Mark R. Hutchinson, Clive McLaughlan, Stefan T. Musolino, Michelle L. Hebart, Robyn Terry, Paul J. Verma, Stefan Hiendleder, Alexandra L. Whittaker
Summary: The study found that circulating miRNA in pigs is not an effective biomarker for emotional state. The challenge remains that current physiological and behavioral indices are either unable to distinguish between positive and negative emotional states, or they are simply not suitable for a production environment.
Review
Biochemical Research Methods
Azim Arman, Mark R. Hutchinson
Summary: This review discusses the major surgical approaches applicable for intrathecal implantation in rodents, along with associated side effects and important preoperative and postoperative considerations.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Article
Neurosciences
Martin E. Gosnell, Vasiliki Staikopoulos, Ayad G. Anwer, Saabah B. Mahbub, Mark R. Hutchinson, Sanam Mustafa, Ewa M. Goldys
Summary: This study successfully validated the feasibility of using hyperspectral autofluorescence imaging and deep learning techniques as a tool to differentiate tissues from nerve injured vs non-injured mice, providing important research and clinical applications prospects.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Pharmacology & Pharmacy
Cong Lin, Hongshuang Wang, Miyuan Zhang, Sanam Mustafa, Yibo Wang, Hongyuan Li, Hang Yin, Mark R. Hutchinson, Xiaohui Wang
Summary: Biased pharmacological modulators offer potential therapeutic benefits by targeting specific receptors with increased efficiency and reduced adverse effects. While biased signaling modulators targeting GPCRs have received attention, the modulation of non-GPCR receptors remains to be explored, including Toll-like receptor 4 (TLR4). Discovery of biased modulators of TLR4 not only provides insights for future development but also potential drug candidates for other non-GPCR receptors.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Immunology
Jacob H. L. Thomas, Liang Lui, Andrew Abell, William Tieu, Andrew A. Somogyi, Juliana E. Bajic, Mark R. Hutchinson
Summary: The study found that reducing TLR signaling pathway can enhance acute analgesic effects, but only male TIR8 deficient mice showed less morphine analgesia. TLR2 and TLR4 deficient mice can prevent analgesic tolerance, but MyD88 animals cannot. Withdrawal behaviors are only protected in TLR2(-/-) mice.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Review
Medicine, General & Internal
Ian Gilron, Maggie Z. X. Xiao, Marielle Balanaser, Meg Carley, Nader Ghasemlou, Michael W. Salter, Mark R. Hutchinson, Dwight E. Moulin, R. Andrew Moore, Amanda Ross-White
Summary: This planned systematic review aims to evaluate the efficacy and adverse effects of glial-modulating drugs in pain management. The study will conduct a detailed search on multiple databases and assess the quality and potential bias of included studies using specific criteria. The findings will provide valuable guidance for pain management strategies.
Review
Neurosciences
Charlotte H. Johnston, Alexandra L. Whittaker, Samantha H. Franklin, Mark R. Hutchinson
Summary: Communication between the central nervous system and the immune system is crucial for the development of chronic pain. Measuring pathological pain state in production animals is challenging, limiting our understanding of chronic pain in animals. Further research into the neuroimmune interface in production animals will benefit human clinical pain management and animal husbandry practices.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Victoria J. Madden, Ncumisa Msolo, Luyanduthando Mqadi, Maia Lesosky, Gillian J. Bedwell, Mark R. Hutchinson, Jonathan Grant Peter, Romy Parker, Andrew Schrepf, Robert R. Edwards, John A. Joska
Summary: This study aims to investigate the relationship between distress, pain, and inflammatory reactivity in HIV-infected individuals. The findings will contribute to a better understanding of pain-related diseases and may lead to new treatment options.
Letter
Clinical Neurology
Graham L. Moseley, Neil Pearson, Roland Reezigt, Victoria J. Madden, Mark R. Hutchinson, Martin Dunbar, Anneke J. Beetsma, Hayley B. Leake, Pete Moore, Laura Simons, Lauren Heathcote, Cormac Ryan, Carolyn Berryman, Amelia K. Mardon, Benedict M. Wand
Article
Biochemistry & Molecular Biology
Edward S. X. Moh, Krishnatej Nishtala, Sameera Iqbal, Vasiliki Staikopoulos, Dilip Kapur, Mark R. Hutchinson, Nicolle H. Packer
Summary: The use of opioids for persistent pain treatment has increased, but it has not improved pain management outcomes. This study investigated the molecular mechanisms of opioids by analyzing proteomics and multiglycomics of cerebral spinal fluid samples from patients receiving long-term intrathecal morphine or baclofen. The study found significant differences in polysialic acid, heparan sulfate glycosaminoglycan, and O-glycan profiles between the two treatment groups, revealing previously undescribed molecular effects of opioid administration and pain management.
Review
Sport Sciences
Timothy L. Miller, Grant L. Jones, Mark Hutchinson, Dharmesh Vyas, James Borchers
Summary: The role of orthopedic team physicians has evolved greatly over the past decade, requiring them to adapt to various challenges and meet the needs and expectations of athlete-patients. With increasing media scrutiny, their work has become more complex and important, and their responsibilities continue to evolve to ensure their relevance and necessity.
CURRENT SPORTS MEDICINE REPORTS
(2021)
Article
Multidisciplinary Sciences
Hongyuan Li, Yinghua Peng, Cong Lin, Xiaozheng Zhang, Tianshu Zhang, Yibo Wang, Yuanpeng Li, Siru Wu, Hongshuang Wang, Mark R. Hutchinson, Linda R. Watkins, Xiaohui Wang
Summary: The study shows that nicotine and its metabolite cotinine inhibit TLR4 via targeting MD2, thus suppressing neuroinflammation, independent of classic neuronal nicotinic acetylcholine receptors.
Review
Public, Environmental & Occupational Health
Susan F. Evans, M. Louise Hull, Mark R. Hutchinson, Paul E. Rolan
Summary: This research delves into the relationship between androgens, endometriosis, and chronic pain, revealing a strong inverse correlation between androgen levels and pelvic and period pain. The study also suggests the potential for alleviating pain by optimizing androgen levels in the treatment of these conditions.
FRONTIERS IN REPRODUCTIVE HEALTH
(2021)
