Article
Biochemistry & Molecular Biology
Piumi B. Wickramasinghe, Shuwen Qian, Lyndsey E. Langley, Chen Liu, Lin Jia
Summary: Accumulating evidence suggests that alcohol overconsumption is associated with insulin resistance, and this study investigated the role of hepatocyte toll-like receptor 4 (TLR4) in alcohol-induced insulin resistance. The findings indicate that hepatocyte TLR4 is both required and sufficient for the development of insulin resistance caused by alcohol overconsumption.
Article
Cardiac & Cardiovascular Systems
Can Gollmann-Tepekoeylue, Michael Graber, Jakob Hirsch, Sophia Mair, Andreas Naschberger, Leo Poelzl, Felix Naegele, Elke Kirchmair, Gerald Degenhart, Egon Demetz, Richard Hilbe, Hao-Yu Chen, James C. Engert, Anna Boehm, Nadja Franz, Daniela Lobenwein, Daniela Lener, Christiane Fuchs, Anna Weihs, Sonja Toechterle, Georg F. Vogel, Victor Schweiger, Jonas Eder, Peter Pietschmann, Markus Seifert, Florian Kronenberg, Stefan Coassin, Michael Blumer, Hubert Hackl, Dirk Meyer, Gudrun Feuchtner, Rudolf Kirchmair, Jakob Troppmair, Markus Krane, Guenther Weiss, Sotirios Tsimikas, George Thanassoulis, Michael Grimm, Bernhard Rupp, Lukas A. Huber, Shen-Ying Zhang, Jean-Laurent Casanova, Ivan Tancevski, Johannes Holfeld
Summary: TLR3 is identified as a central molecular regulator of calcification in valvular interstitial cells, and BGN is revealed as a new endogenous agonist of TLR3. BGN activates TLR3 through XYLT1-dependent posttranslational modification and induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through TLR3-dependent induction of type I interferons.
Article
Neurosciences
Liang Liu, Tian-Ce Xu, Zi-Ai Zhao, Nan-Nan Zhang, Jing Li, Hui-Sheng Chen
Summary: TLR4 signaling in neurons plays a crucial role in neuronal death and neuroinflammatory responses following brain ischemia. Deletion of TLR4 reduces neuronal death and intracellular Ca2+ influx induced by oxygen and glucose deprivation or lipopolysaccharide treatment. TLR4 interacts with NMDAR2B and affects the interaction between nNOS and PSD-95, contributing to ischemic injury.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xinghua Wang, Anthony Pham, Lu Kang, Sierra A. Walker, Irina Davidovich, Dalila Iannotta, Sarvam P. TerKonda, Shane Shapiro, Yeshayahu Talmon, Si Pham, Joy Wolfram
Summary: Extracellular vesicles (EVs) are nanoparticles released by cells that transfer biomolecules between cells. MicroRNAs (miRNAs/miRs) in EVs play a significant role in modulating signaling pathways in recipient cells. This study shows that miR-451a, abundant in EVs from adipose tissue, can suppress pro-inflammatory cytokines and enhance anti-inflammatory cytokines in the TLR4 pathway.
Review
Cell Biology
Elise E. Bruning, Janet K. Coller, Hannah R. Wardill, Joanne M. Bowen
Summary: TLR4 is a highly conserved protein involved in innate immunity with distinct roles in epithelial and immune cells throughout the gastrointestinal tract. While epithelial cell expression of TLR4 contributes to maintaining homeostasis, promoting immunoglobulin A production, and regulating permeability, immune cell expression is centered on maturation of dendritic cells and priming the adaptive immune system. However, further research is needed to fully understand the impact of site-specific TLR4 expression on inflammation and disease progression.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Plant Sciences
Min Cai, You-cai Xu, Bo Deng, Jun-Bang Chen, Ting-Fang Chen, Ke-Feng Zeng, Si Chen, Sui-hui Deng, Zhang-bin Tan, Wen-jun Ding, Shuang-wei Zhang, Bin Liu, Jing-zhi Zhang
Summary: This study found that GL extract and its active constituent LicoA exerted anti-inflammatory effects by targeting TLR4 directly, reducing inflammatory damage and inhibiting TLR4 signaling activation.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Oncology
Federica Liotti, Maria Marotta, Daniela Sorriento, Emanuela Pone, Francesco Morra, Rosa Marina Melillo, Nella Prevete
Summary: TLR7, PRR, and FPR1 have been identified as potential regulators in inhibiting angiogenesis and inflammation resolution in cancer. The study suggests new strategies for the treatment of lung and gastric cancer.MAPK and STAT3 signaling play a crucial role in these activities.
Article
Biochemistry & Molecular Biology
Haein Lee, Eunha Kim, Seyun Kim
Summary: In response to LPS stimulation, the levels of IPMK in macrophages decrease due to the binding of miR-181c to the 3'UTR of IPMK mRNA, which leads to the suppression of TLR4 signaling and inflammation. Deletion of the miR-181c-binding site prevents the downregulation of IPMK levels and reduces the activation of TRAF6 and the expression of proinflammatory cytokines.
Article
Biochemistry & Molecular Biology
Natsumi Ogawa, Shingo Nakajima, Kenya Tamada, Natsuki Yokoue, Haruki Tachibana, Miwa Okazawa, Takahiro Oyama, Hideaki Abe, Hiroaki Yamazaki, Atsushi Yoshimori, Akira Sato, Takanori Kamiya, Takehiko Yokomizo, Fumiaki Uchiumi, Takehiko Abe, Sei-ichi Tanuma
Summary: The spasmolytic drug trimebutine has shown potential as an anti-inflammatory agent in experiments, reducing the production of various proinflammatory factors and significantly decreasing mortality in a mouse model of sepsis. Studies have found that trimebutine exerts its anti-inflammatory effects by inhibiting TLR signaling pathways and NF-kappa B activity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Biochemistry & Molecular Biology
Patricia G. G. Valles, Andrea Fernanda Gil Lorenzo, Rodrigo D. D. Garcia, Valeria Cacciamani, Maria Eugenia Benardon, Valeria Victoria Costantino
Summary: Acute kidney injury (AKI) is a common and devastating condition with no effective pharmacological treatment. Toll-like receptor 4 (TLR4) and its ligands play a crucial role in the pathogenesis of AKI by mediating inflammatory responses. Excessive activation of TLR4 can lead to chronic inflammation. This review discusses the role of TLR4 in ischemic/reperfusion-induced AKI and sepsis-associated AKI, as well as its potential signaling patterns in kidney injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Saahithh Redddi Patlola, Gary Donohoe, Declan P. McKernan
Summary: Toll-like receptors (TLRs) are pattern recognition receptors that protect the brain from self and foreign antigens/pathogens and can elicit a harmful or beneficial immune response. TLR activation has been associated with neurodegenerative diseases and cytokine imbalance in schizophrenia. This review explores the current literature on TLRs, their potential role in schizophrenia pathogenesis, factors affecting TLR activity and their impact on cognitive performance in schizophrenia.
Article
Immunology
Huanyu Jiang, Yubiao Zhang, Geliang Hu, Xiaobin Shang, Jianghua Ming, Ming Deng, Yaming Li, Yonggang Ma, Shiqing Liu, Yan Zhou
Summary: The study reveals the important role of surfactant protein D (SP-D) in regulating inflammation and immune response in osteoarthritis (OA). SP-D exhibits chondroprotective properties by downregulating inflammation-related genes, suppressing cytokine production, and reducing infiltration of inflammatory cells. The binding of SP-D to the TLR4/MD-2 complex further inhibits TLR4-mediated signaling activation. These findings suggest that SP-D has a beneficial effect in attenuating inflammation and preserving cartilage integrity in OA.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Bahareh Kashani, Zahra Zandi, Atieh Pourbagheri-Sigaroodi, Davood Bashash, Seyed H. Ghaffari
Summary: The TLR family is crucial for pattern recognition in innate immunity, with TLR4 playing a significant role in inflammatory diseases and cancer. Aberrant expression of TLR4 in tumors is closely associated with tumorigenesis, progression, and drug resistance. TLR4 inhibitors show promise in cancer therapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Immunology
Huanghui Wu, Han Bao, Cong Liu, Qiao Zhang, Ailing Huang, Minxue Quan, Chunhui Li, Ying Xiong, Guozhong Chen, Lichao Hou
Summary: This study investigated the role and mechanism of extracellular nucleosomes and histones, as damage-associated molecular patterns (DAMPs), in progressive neuroinflammation and chronic stress-related emotional disorders. It found that extracellular nucleosomes accelerate microglial inflammation via Clec2d and TLR9, contributing to chronic stress-induced emotional disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kiran Shabir, Seley Gharanei, Sophie Orton, Vanlata Patel, Parbata Chauhan, Emmanouil Karteris, Harpal S. Randeva, James E. Brown, Ioannis Kyrou
Summary: Adipose tissue functions as an endocrine organ by secreting various adipokines that regulate metabolism and other physiological processes. The altered secretion of adipokines has been associated with obesity and cardio-metabolic diseases. Asprosin, a recently discovered adipokine, is elevated in cardio-metabolic diseases and has pro-inflammatory effects, at least in part through the TLR4 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Paolo Bima, Giorgia Montrucchio, Valeria Caramello, Francesca Rumbolo, Stefania Dutto, Sarah Boasso, Anita Ferraro, Luca Brazzi, Enrico Lupia, Adriana Boccuzzi, Giulio Mengozzi, Fulvio Morello, Stefania Battista
Summary: This prospective observational study aimed to evaluate the prognostic value of mid-regional proADM (MR-proADM) in septic patients presenting to the emergency department (ED). The results showed that MR-proADM levels at presentation and after 72 hours were predictive of 28-day survival, and the change in MR-proADM levels over time provided additional prognostic information. MR-proADM(%change) was identified as a significant outcome predictor, providing up to 80% of added prognostic value.
Article
Biochemistry & Molecular Biology
Emiliano Laudadio, Giovanna Mobbili, Leonardo Sorci, Roberta Galeazzi, Cristina Minnelli
Summary: The discovery of mutations within the kinase domain of the EGFR gene has revolutionized targeted therapy for NSCLC. However, the impact of these mutations on the conformation and stability of EGFR-ATP complexes is still not fully understood. In this study, we used dynamic docking simulations to investigate the effect of mutations on the Michaelis-Menten constant and observed a correlation with ATP affinities. Additionally, we found that ATP binding is the first step in promoting the conformational shift to the active state and highlighted the contribution of water hydrogen bond and water-bridge networks in the modulation of ATP affinity. These findings provide valuable insights for cancer therapy and personalized medicine development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Nutrition & Dietetics
Ilario Ferrocino, Marianna Pellegrini, Chiara D'Eusebio, Ilaria Goitre, Valentina Ponzo, Maurizio Fadda, Rosalba Rosato, Giulio Mengozzi, Guglielmo Beccuti, Fabio Dario Merlo, Farnaz Rahimi, Isabella Comazzi, Luca Cocolin, Ezio Ghigo, Simona Bo
Summary: The metabolic benefits of time-restricted eating (TRE) in humans are statistically significant but not clinically relevant. This study compared the effects of a TRE regimen with a time-unrestricted (TUE) regimen on patients with obesity. The results show that TRE led to a slightly greater weight loss compared to TUE, but there were no significant differences in other variables. The changes in gut microbiota composition induced by TRE were of uncertain clinical significance.
Review
Medicine, General & Internal
Giorgia Montrucchio, Eleonora Balzani, Davide Lombardo, Alice Giaccone, Anna Vaninetti, Giulia D'Antonio, Francesca Rumbolo, Giulio Mengozzi, Luca Brazzi
Summary: MR-proADM levels at ICU admission appear to predict mortality among critical COVID-19 patients. Further prospective studies focused on critically ill patients are needed to establish a reliable cut-off value.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Iacopo Gesmundo, Francesca Pedrolli, Nicoletta Vitale, Alessia Bertoldo, Giulia Orlando, Dana Banfi, Giuseppina Granato, Ramesh Kasarla, Federico Balzola, Silvia Deaglio, Renzhi Cai, Wei Sha, Mauro Papotti, Ezio Ghigo, Andrew Schally, Riccarda Granata
Summary: This study found that GHRH antagonist MIA-690 enhances the antitumor effect of cisplatin and pemetrexed in pleural mesothelioma by inhibiting proliferative and oncogenic pathways, as well as reducing inflammatory pathways and expression of oxidative, angiogenic, tumorigenic markers, and growth factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Gabriele Minazzato, Elisa Marangoni, Carlo Fortunato, Riccardo Petrelli, Loredana Cappellacci, Fabio Del Bello, Leonardo Sorci, Massimiliano Gasparrini, Francesco Piacente, Santina Bruzzone, Nadia Raffaelli
Summary: Maintaining an adequate NAD(+) pool is crucial for cell survival, especially in tumor cells. Inhibition of NAD(+) biosynthesis through targeting enzymes such as NAMPT and NAPRT is considered a promising therapeutic strategy. A new continuous coupled fluorometric assay was developed to screen NAPRT inhibitors by measuring NADH formation. Several compounds were identified as NAPRT inhibitors and were shown to sensitize cancer cells to NAMPT inhibition, decreasing viability and intracellular NAD(+) levels.
Article
Biochemistry & Molecular Biology
Federico Ponzetto, Mirko Parasiliti-Caprino, Fabio Settanni, Antonello Nonnato, Giulio Mengozzi, Ezio Ghigo, Roberta Giordano
Summary: The simultaneous measurement of dexamethasone and cortisol has shown to improve the diagnostic performance of the overnight dexamethasone-suppression test. Additionally, monitoring the levels of corticosteroid drugs can help investigate unexpected changes in steroid hormone levels. This study developed and validated an LC-MS/MS method for quantifying cortisol, cortisone, dexamethasone, and other corticosteroids in serum/plasma samples. The method was successfully applied to patients undergoing the dexamethasone-suppression test and those receiving immunosuppressive treatment after kidney transplant.
Article
Agriculture, Dairy & Animal Science
Barbara Bruno, Cristiana Maurella, Paola Gianella, Giulio Mengozzi, Erica Ferraris, Antonio Borrelli
Summary: This study observed the haemostasis characteristics in dogs undergoing surgery for malignancies, using rotational thromboelastometry and thrombin generation. The results showed a trend of hypercoagulability 24 hours after surgery and a return to pre-surgery state after 2 weeks.
Article
Chemistry, Medicinal
Cecilia Baldassarri, Gianfabio Giorgioni, Alessandro Piergentili, Wilma Quaglia, Stefano Fontana, Valerio Mammoli, Gabriele Minazzato, Elisa Marangoni, Massimiliano Gasparrini, Leonardo Sorci, Nadia Raffaelli, Loredana Cappellacci, Riccardo Petrelli, Fabio Del Bello
Summary: The inhibition of NAD biosynthesis is a potential therapeutic approach against cancer, while boosting NAD biosynthesis is relevant for neurodegeneration and metabolic diseases. Targeting NAMPT and NAPRT enzymes that regulate NAD biosynthesis has shown promise. In this study, new NAPRT modulators were identified as potential activators or inhibitors, with compound 18 showing good pharmacokinetic properties and behaving as an inhibitor towards NA and PRPP. Docking studies were performed to understand the structural basis, and a preliminary pharmacophore model shed light on the transition from inhibitors to activators.
Article
Biochemistry & Molecular Biology
Sara Boumya, Silvia Fallarini, Sonia Siragusa, Giovanni Petrarolo, Silvio Aprile, Valentina Audrito, Concettina La Motta, Silvia Garavaglia, Laura Moro, Giulia Pinton
Summary: Aldehyde dehydrogenase 1A3 (ALDH1A3) has been linked to poor prognosis in malignant pleural mesothelioma (MPM). Inhibition of ALDH1A3 using NR6 resulted in the accumulation of toxic aldehydes, DNA damage, CDKN2A expression, and cell growth arrest. NR6 treatment also affected the tumor microenvironment by altering IL6, CXCL8, and IL-8 levels, and shifting cell fate from senescence to apoptosis. Understanding the role of ALDH1A3 in MPM cells and the tumor microenvironment could lead to potential new treatments for this cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Federico Ponzetto, Mirko Parasiliti-Caprino, Iacopo Gesmundo, Lorenzo Marinelli, Antonello Nonnato, Raul Nicoli, Tiia Kuuranne, Giulio Mengozzi, Ezio Ghigo, Fabio Settanni
Summary: The urinary steroidal module of Athlete Biological Passport is currently used to detect anti-doping rule violations related to the abuse of endogenous anabolic androgenic steroids. However, alternative strategies such as the measurement of blood concentrations of endogenous steroid hormones by LC-MS have been proposed due to limitations of the urine test. This study presents a UHPLC-MS/MS method for quantifying major circulating steroid hormones and their metabolites, showing promising results for measuring blood steroid profile markers.
Article
Cell Biology
Christian Leveque, Yves Maulet, Qili Wang, Marion Rame, Lea Rodriguez, Sumiko Mochida, Marion Sangiardi, Fahamoe Youssouf, Cecile Iborra, Michael Seagar, Nicolas Vitale, Oussama El Far
Summary: V-ATPase plays a crucial role in synaptic vesicle acidification and synaptic transmission. The V1 sector rotation drives proton transfer through the V0 sector, and the V0 subunits V0a and V0c interact with SNARE proteins. The soluble subunit V0d is essential for the proton transfer activity of V-ATPase and can inhibit the interaction between V0c and SNAREs.
Article
Biochemistry & Molecular Biology
Qili Wang, Alexander Wolf, Sebahat Ozkan, Ludovic Richert, Yves Mely, Sylvette Chasserot-Golaz, Stephane Ory, Stephane Gasman, Nicolas Vitale
Summary: Although the importance of lipids in cells and human diseases is increasingly recognized, their specific roles, especially in neurosecretion, are still largely unknown. Recent research has highlighted the critical role of lipid localization and fusogenic lipids in membrane fusion, but the regulatory mechanisms behind lipid synthesis and neurosecretion are poorly understood.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Cell Biology
Irene Fiorilla, Simona Martinotti, Alberto Maria Todesco, Gregorio Bonsignore, Maria Cavaletto, Mauro Patrone, Elia Ranzato, Valentina Audrito
Summary: Malignant pleural mesothelioma (MPM) is a lethal and rare cancer with increasing incidence worldwide. Asbestos exposure causes MPM through mechanisms including chronic inflammation, oxidative stress, and aberrant signaling. The tumor microenvironment characteristics, such as chronic inflammation, hypoxia, and metabolic changes, support tumor aggressiveness and modulate immune responses. Understanding these interactions provides potential therapeutic targets in MPM.
Article
Health Care Sciences & Services
Francesco Chiara, Sarah Allegra, Jacopo Mula, Maria Paola Puccinelli, Giuliana Abbadessa, Giulio Mengozzi, Silvia De Francia
Summary: Orotic acid is an intermediate metabolite of pyrimidine nucleotide biosynthesis and plays a role in various physiological processes. Measurement of its concentration in urine can help diagnose hereditary metabolic diseases. This study found that females had higher levels of orotic acid in pediatric age, suggesting potential gender differences in pyrimidine intermediate biosynthesis. These findings have implications for understanding the biochemical aspects of pyrimidine biosynthesis and its related disorders.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
