Review
Clinical Neurology
Aislinn D. Maguire, John R. Bethea, Bradley J. Kerr
Summary: Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. Animal models such as EAE mice are used to study the complex mechanisms of neuropathic pain in MS, with TNFα identified as a critical factor. Current TNFα-targeted therapies indiscriminately block both pro-inflammatory and pro-homeostatic pathways, making them ineffective in treating MS.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alejandro Speck-Planche, Valeria V. Kleandrova, Marcus T. Scotti
Summary: Inflammation is a complex biological response of body tissues to damaging stimuli, and dysregulated inflammation led by biomolecular mediators can play a detrimental role in various medical conditions. Computational approaches can accelerate the search for anti-inflammatory drugs, with this study developing a virtual screening model with an accuracy exceeding 88% to identify and validate agency-regulated chemicals as versatile anti-inflammatory therapeutics.
Review
Cell Biology
Begona Canovas, Angel R. Nebreda
Summary: The ability of cells to cope with various stressful situations is crucial for survival, with p38 alpha kinase playing a key role in the cellular stress response. Understanding the diversity of p38 alpha substrates, their mechanisms, and their connections to specific cellular functions is important for insights into physiology and pathology. Dysregulation of the p38 alpha pathway has been linked to diseases such as inflammation, immune disorders, and cancer.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Enkhtuya Radnaa, Lauren Richardson, Brett Goldman, Jared K. Burks, Tuvshintugs Baljinnyam, Natasha Vora, Hui-Juan Zhang, Elizabeth A. Bonney, Arum Han, Ramkumar Menon
Summary: This study investigated the impact of oxidative stress on p38 MAPK signaling and cell fate, using amnion epithelial cells. The results showed that excessive activation of p38 can have adverse effects on cell behavior and tissue homeostasis.
Article
Cell Biology
Anna Kovalchuk, Bo Wang, Dongping Li, Rocio Rodriguez-Juarez, Slava Ilnytskyy, Igor Kovalchuk, Olga Kovalchuk
Summary: The study suggests that novel cannabis extracts have the potential to effectively downregulate key pro-inflammatory cytokines and pathways involved in inflammation and fibrosis, presenting a promising treatment option for COVID-19, rheumatological diseases, as well as inflammatory aging-related conditions.
Article
Chemistry, Multidisciplinary
Sumera Qasim, Alamgeer, Muhammad Saleem, Nasser Hadal Alotaibi, Syed Nasir Abbas Bukhari, Khalid Saad Alharbi, Hafiz Muhammad Irfan, Rukhsana Anwar
Summary: The study demonstrated that prazosin exhibits significant antiarthritic effects by reducing protein denaturation, stabilizing red blood cell membrane, and alleviating paw swelling in both formaldehyde-induced arthritis and CFA-induced arthritis models. It also maintains normal hematological and biochemical profiles. Furthermore, prazosin may potentially inhibit TNF-alpha to exert its strong antiarthritic potential.
Article
Immunology
Fengyuan Mandy Yang, Liya Shen, Dengxia Denise Fan, Yaqin Bai, Bizhou Li, Jongdae Lee
Summary: YAP9 is identified as an essential negative regulator of potent inflammatory stimuli like TNFα, IL-1β, and LPS, working in conjunction with A20 to suppress inflammatory responses. YAP9 and A20 utilize different structural domains to suppress inflammatory signaling, and synthetic peptides mimicking their functions can effectively suppress proinflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Ayelen Ivana Pesce Viglietti, Franco Agustin Sviercz, Cinthya Alicia Marcela Lopez, Rosa Nicole Freiberger, Jorge Quarleri, Maria Victoria Delpino
Summary: Kingella kingae is an emerging pathogen that causes septic arthritis, osteomyelitis, and bacteremia in children aged 6 to 48 months. Infection with K. kingae directly stimulates osteoclastogenesis and indirectly through a potent pro-inflammatory response that drives macrophages to become functional osteoclasts. Additionally, the osteoclastogenic capability of K. kingae is counteracted by their outer membrane vesicles in a concentration-dependent manner.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Manivel Rengasamy, Anna Marsland, Lora McClain, Tessa Kovats, Thomas Walko, Lisa Pan, Rebecca B. Price
Summary: The study found that in adolescents receiving standard-of-care community treatment, TNF alpha levels were positively correlated with depression severity and anhedonia symptoms, with higher baseline TNF alpha levels predicting more severe depression symptoms in the future. However, no association was found between changes in clinical measures and changes in cytokine levels over time.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Sachin Honnenahalli Rajegowda, Athahalli Honnagirigowda Sneharani
Summary: This study characterized a novel protease inhibitor (PIs) isolated from Caesalpinia decapetala seeds and investigated its mechanism of action. The purified PIs showed promising results in curbing inflammation, by inhibiting inflammatory response and reducing the release of inflammatory mediators.
CELL BIOCHEMISTRY AND FUNCTION
(2023)
Article
Biochemistry & Molecular Biology
Tatyana P. Makalish, Ilya O. Golovkin, Volodymyr V. Oberemok, Kateryna V. Laikova, Zenure Z. Temirova, Olesya A. Serdyukova, Ilya A. Novikov, Roman A. Rosovskyi, Andrey I. Gordienko, Evgeniya Yu. Zyablitskaya, Elvina A. Gafarova, Kseniya A. Yurchenko, Iryna I. Fomochkina, Anatoly V. Kubyshkin
Summary: The study demonstrates the potential of Cytos-11 antisense oligonucleotide in treating rheumatoid arthritis by effectively suppressing TNF-alpha gene expression, reducing joint inflammation, and inhibiting pannus development, showing comparable results to adalimumab.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Elisa Rubino, Andrea Marcinno, Alberto Grassini, Elisa Maria Piella, Fabio Ferrandes, Fausto Roveta, Silvia Boschi, Aurora Cermelli, Salvatore Gallone, Lidia Savi, Innocenzo Rainero
Summary: Migraine is a common disorder with unsatisfactory response to acute pain-relieving therapies. Functional polymorphism in the TNF-alpha gene is associated with the efficacy of NSAID administration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Liang Yu, Kai Yang, Xiaoyan He, Min Li, Lin Gao, Yunhong Zha
Summary: This study predicted candidate drugs for sepsis treatment using bioinformatics analysis and validated linifanib as an effective drug in cellular and mouse models. Linifanib protected cells from necroptosis and rescued SIRS mice from shock and death. These findings suggest the potential clinical utility of linifanib in septic patients.
CELL DEATH DISCOVERY
(2023)
Article
Oncology
Constandina E. O'Connell, Alex Vassilev
Summary: The study revealed that PIKfyve and p38MAPK cooperate to regulate lysosome homeostasis, and their combined inhibition synergistically blocks autophagy to reduce cancer cell viability in vitro and in vivo.
Article
Rheumatology
Takahisa Gono, Yuka Okazaki, Masataka Kuwana
Summary: An antiviral proinflammatory network orchestrated primarily by activated monocytes/macrophages might be responsible for cytokine storm in patients with anti-MDA5-associated interstitial lung disease.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)