Article
Biochemistry & Molecular Biology
Uxia Regueiro, Maite Lopez-Lopez, Ruben Varela-Fernandez, Tomas Sobrino, Elio Diez-Feijoo, Isabel Lema
Summary: Keratoconus (KC) is a corneal disorder closely related to dysregulation of Lactoferrin (LTF) and overexpression of Toll-like Receptors 2 (TLR2). This study explores the association between these two biomarkers, providing insights into KC pathophysiology and potential therapeutic approaches. The study quantified LTF concentrations in serum and tear samples from KC patients and controls, and conducted correlation analysis with immunoinflammatory mediators and KC-associated tomographic parameters. In vitro experiments using cell cultures were also conducted to investigate the impact of LTF treatment on TLR2 expression and functionality. The results showed decreased LTF levels in KC patients compared to controls, indicating a strong correlation with TLR2 overexpression, inflammatory mediator upregulation, and KC severity. In stimulated cell cultures, TLR2 expression was reduced after LTF treatment, along with decreased secretion of SEAP and IL-8. Overall, the dysregulation of LTF and TLR2 in the ocular surface of KC patients contributes to KC severity by maintaining a chronic immune-inflammatory state, suggesting the potential of LTF as a therapeutic approach for KC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Xiaohong Cen, Baoqu Wang, Yuqing Liang, Yanlin Chen, Yu Xiao, Shaohua Du, Kutty Selva Nandakumar, Hang Yin, Shuwen Liu, Kui Cheng
Summary: This study revealed the clinical relevance of TLR3 upregulation in human atherosclerosis and its contribution to the disease processes. Inhibition of TLR3 led to reduced foam cell formation and atherosclerotic burden, suggesting TLR3 as a potential novel target for atherosclerosis therapy.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Neurosciences
Anubha Chaudhary, Parul Mehra, Anand K. Keshri, Suraj S. Rawat, Amit Mishra, Amit Prasad
Summary: The new paradigms of psychiatric disorders pathogenesis are inclined towards chronic inflammation, affecting neuronal networks. Inflammation is strongly associated with depression and mediated by toll-like receptors (TLRs) in neurobiology. TLRs and their signaling pathways play a key role in immune regulation to stress and infections. This review summarizes the role of TLRs in psychotic disorders and acquired epilepsy, as well as their potential in immune response mediated through antidepressant therapies and TLRs polymorphism associated with various psychiatric disorders.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Cell Biology
Yue Zhu, Xinzhi Peng, Qianlei Zhou, Langping Tan, Cheng Zhang, Shaojian Lin, Miaoyun Long
Summary: This study revealed that the expression of six transmembrane epithelial antigen of the prostate 2 (STEAP2) is downregulated in papillary thyroid cancer (PTC) tissues. Low STEAP2 expression is associated with aggressive clinicopathological characteristics and poor prognosis in PTC patients. The METTL3-mediated STEAP2 N6-methyladenosine (m6A) modification plays a critical tumor-suppressive role in PTC progression. The METTL3-STEAP2 axis may serve as a potential therapeutic molecular target against PTC.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Isaac Rosado-Sanchez, Manjurul Haque, Kevin Salim, Madeleine Speck, Vivian C. W. Fung, Dominic A. Boardman, Majid Mojibian, Giorgio Raimondi, Megan K. Levings
Summary: Tregs expressing chimeric antigen receptors (CAR-Tregs) were studied to understand the relationship between CAR structure and Treg function. CD28-encoding CARs showed advantages in xenogeneic, immunodeficient mice, but the interactions with antigen-presenting cells (APCs) and donor specific antibodies were not fully represented. In vitro, CD28-encoding CARs had superior antigen-specific suppression, proliferation, and cytokine production. However, in vivo, Tregs expressing CARs encoding CD28, ICOS, programmed cell death 1, and GITR extended skin allograft survival, while CARs encoding 4-1BB or OX40 did not. Analysis of a CAR encoding CD3 zeta but no costimulatory domain revealed that exogenous costimulation from APCs can compensate for the lack of a CAR-encoded CD28 domain. This study has important implications for the design of CARs for clinical use in Tregs.
Article
Agriculture, Dairy & Animal Science
Wan Xie, Yang Xue, Xiaokun Song, Hongzhu Zhang, Guangjun Chang, Xiangzhen Shen
Summary: This study found that LPS activates TLR4 and inhibits FOXA2 expression, leading to NF-kappa B-mediated inflammation, ER stress, autophagy, and apoptosis. Inhibiting TLR4 and increasing FOXA2 expression can alleviate LPS-induced inflammation, ER stress, autophagy, and apoptosis, maintaining cellular homeostasis.
JOURNAL OF DAIRY SCIENCE
(2023)
Article
Clinical Neurology
Pinku Mani Talukdar, Fazal Abdul, Michael Maes, Michael Berk, Ganesan Venkatasubramanian, Bindu M. Kutty, Monojit Debnath
Summary: Prenatal infection-induced maternal immune activation (MIA) may trigger TLR and inflammasome pathways, increasing the risk of schizophrenia-like behaviors in the offspring later in life.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Hijai R. Shin, Y. Rose Citron, Lei Wang, Laura Tribouillard, Claire S. Goul, Robin Stipp, Yusuke Sugasawa, Aakriti Jain, Nolwenn Samson, Chun-Yan Lim, Oliver B. Davis, David Castaneda-Carpio, Mingxing Qian, Daniel K. Nomura, Rushika M. Perera, Eunyong Park, Douglas F. Covey, Mathieu Laplante, Alex S. Evers, Roberto Zoncu
Summary: LYCHOS, a lysosomal cholesterol signaling protein, senses cholesterol concentration and interacts with mTORC1 to regulate cellular growth and metabolism.
Article
Biochemistry & Molecular Biology
Rui Sun, Pei-Pei Zhang, Xiang-Qin Weng, Xiao-Dong Gao, Chuan-Xin Huang, Li Wang, Xiao-Xia Hu, Peng-Peng Xu, Lin Cheng, Lu Jiang, Di Fu, Bin Qu, Yan Zhao, Yan Feng, Hong-Jing Dou, Zhong Zheng, Wei-Li Zhao
Summary: The overexpression of miR130b in DLBCL is associated with disease progression and the tumor microenvironment, influencing treatment outcomes and survival rates of DLBCL patients by modulating the interaction between tumor cells and Th17 cells via OX40/OX40L pathway.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Review
Biochemistry & Molecular Biology
Arturo Orlacchio, Pellegrino Mazzone
Summary: Pancreatic cancer is a lethal form of cancer characterized by its aggressiveness and metastatic potential. Toll-like receptors play a pivotal role in inflammation and immune response, and can be potential targets for cancer therapy. Studies have shown that TLRs play an important role in the progression of pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Ibrahim Fouad Elesh, Mohamed Ali Marey, Mohammed Ali Zinnah, Ihshan Akthar, Tomoko Kawai, Fayrouz Naim, Wael Goda, Abdel Rahman A. Rawash, Motoki Sasaki, Masayuki Shimada, Akio Miyamoto
Summary: The research characterized the impact of pathogen-derived TLR2/4 ligands on the immune crosstalk between sperm and bovine endometrial epithelium. Low levels of PGN inhibited sperm-induced inflammatory responses and impaired sperm phagocytosis by PMNs. TLR2 signaling acts as a shared pathway for PGN and sperm recognition, potentially leading to impairment of uterine clearance and embryo receptivity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Dhivya Sridaran, Surbhi Chouhan, Kiran Mahajan, Arun Renganathan, Cody Weimholt, Shambhavi Bhagwat, Melissa Reimers, Eric H. Kim, Manish K. Thakur, Muhammad A. Saeed, Russell K. Pachynski, Markus A. Seeliger, W. Todd Miller, Felix Y. Feng, Nupam P. Mahajan
Summary: This study identifies a T-cell pathway that leads to the inactivation of tumor-infiltrating T cells and resistance to immune therapy, thus explaining the limited effectiveness of immune checkpoint blockade (ICB) in solid tumors. Activation of the oncogenic tyrosine kinase ACK1 enhances the function of CSK, a negative regulator of T-cell activation, and constrains the activation of T cells. Inhibition of ACK1 effectively suppresses ICB-resistant tumors, providing new insights into ICB resistance mechanisms and potential targets for expanding ICB therapy.
NATURE COMMUNICATIONS
(2022)
Article
Food Science & Technology
Ines Abad, Andrea Sanguesa, Maria Ubieto, Juan J. Carraminana, Maria D. Perez, Berta Buey, Jose E. Mesonero, Laura Grasa, Lourdes Sanchez
Summary: Milk is a valuable source of bioactive proteins that have defensive properties for protecting newborns. This study investigated the antibacterial activity of bovine milk lactoferrin (LF) against the emergent pathogen Cronobacter sakazakii and its effects on oxidative stress and Toll-like receptor expression. The results showed that LF exhibited clear antibacterial activity against C. sakazakii and inhibited its adhesion and internalization into Caco-2/TC7 cells. LF also reduced oxidative stress and altered Toll-like receptor expression, particularly the downregulation of TLR4. These findings highlight the potential of LF as an ingredient in functional foods.
INTERNATIONAL DAIRY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Jie Zhang, Lei Cao, Amy Gao, Ruiqing Ren, Liwen Yu, Qian Li, Yapeng Liu, Wenqian Qi, Yonghao Hou, Wenhai Sui, Guohai Su, Yun Zhang, Cheng Zhang, Meng Zhang
Summary: Innate immunity is the first defense line against pathogenic microorganisms, and Toll-like receptor (TLR)-mediated inflammatory responses play a crucial role. However, the regulatory mechanisms of TLRs in innate immunity are not well understood. This study showed that the E3 ligase Ring finger protein 99 (RNF99) plays a role in regulating TLR-mediated inflammatory responses and its deficiency enhances inflammatory cytokine expression in macrophages. Mechanistically, RNF99 interacts with and degrades the regulatory protein TAB2, thus regulating TLR-mediated inflammatory signaling. These findings provide new insights into TLR signal transduction and offer potential approaches for preventing bacterial infections and inflammatory diseases.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Pediatrics
Tianjing Liu, Haifeng Zong, Xiaoyu Chen, Sihang Li, Ziyun Liu, Xuewei Cui, Guoqiang Jia, Yongyan Shi
Summary: The study indicates that necroptosis is an essential pathological process of NEC, with TLR4 possibly acting as a stimulator. Inhibiting intestinal cell necroptosis may be a beneficial strategy in the treatment of NEC.
PEDIATRIC RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Valeria Fedeli, Alessandra Cucina, Simona Dinicola, Gianmarco Fabrizi, Angela Catizone, Luisa Gesualdi, Simona Ceccarelli, Abdel Halim Harrath, Saleh H. Alwasel, Giulia Ricci, Paola Pedata, Mariano Bizzarri, Noemi Monti
Summary: This study found that simulated microgravity impairs the function of fibroblasts and disrupts the interaction between cells and their microenvironment, resulting in abnormal tissue structure. The conversion of fibroblasts into myofibroblasts is impaired, and their migratory properties are inhibited, affecting the normal interaction between fibroblasts and keratinocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Daniela Latorre, Sallusto Federica, Claudio L. A. Bassetti, Ulf Kallweit
Summary: Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. Diagnosis and treatment of the disease remain challenging due to its clinical heterogeneity and lack of understanding of its underlying mechanisms. However, significant progress has been made in recent years, opening new perspectives for the field.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Giuseppe Giannini, Irene Ragusa, Giulia Nerina Nardone, Sara Soldi, Marina Elli, Piera Valenti, Luigi Rosa, Emanuele Marra, Daniela Stoppoloni, Emilio Merlo Pich
Summary: This study presents a mucoadhesive gel containing probiotics capable of slow release of bacteria to prevent and treat periodontitis. The results show significant and stable release of the bacterial mixture in vitro and improved tissue pathology in a mouse model of periodontitis.
INTERNATIONAL JOURNAL OF DENTISTRY
(2022)
Article
Biochemistry & Molecular Biology
Luigi Rosa, Antimo Cutone, Maria Pia Conte, Elena Campione, Luca Bianchi, Piera Valenti
Summary: This article reviews the antiviral activity of lactoferrin (Lf) against various types of viruses, including SARS-CoV-2. The study found that oral administration of Lf can counteract COVID-19 pathogenesis in the early stage of SARS-CoV-2 infection and have effects on various physiological processes such as inflammation, iron ion regulation, and coagulation balance. Furthermore, the article reveals the binding mechanisms of Lf to host cells and viral particle surface components. In summary, these studies support the use of Lf as an oral medication for treating COVID-19 or as an adjuvant for symptomatic treatment.
Review
Immunology
Daniela Latorre
Summary: According to the World Health Organization, SARS-CoV-2 has infected over 400 million people globally and caused over 5 million deaths. New-onset neurological and neuropsychiatric symptoms have been increasingly reported in COVID-19 patients, potentially posing a significant public health threat. Evidence suggests that SARS-CoV-2 infection may trigger an autoimmune response, which could contribute to neurological disorders in COVID-19 patients.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Editorial Material
Chemistry, Multidisciplinary
Maria A. Mariggio, Giulia Ricci
APPLIED SCIENCES-BASEL
(2022)
Editorial Material
Immunology
Daniela Latorre, Annika Hausmann, Sinduya Krishnarajah, Jorieke Weiden, Pascal Naf, Anna Estrada Brull
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Valeria Fedeli, Angela Catizone, Alessandro Querqui, Vittorio Unfer, Mariano Bizzarri
Summary: Polycystic ovarian syndrome (PCOS) is a common endocrinological disorder in women, characterized by chronic anovulation/oligomenorrhea, ovarian cysts, and hyperandrogenism. Recent research has shown that inositol isomers, myo-Inositol and D-Chiro-Inositol, have pharmacological effects in managing PCOS symptoms and fertility. However, the specific biological functions of these isomers need further investigation, as D-Chiro-Inositol stimulates androgen synthesis while myo-Inositol activates FSH response and aromatase activity. Combination therapy of the two isomers in the physiological ratio has been found to be beneficial for PCOS patients. Insulin hypersensitivity is likely a shared feature of PCOS ovaries, and the imbalance of D-Chiro-Inositol may contribute to the pathogenesis of PCOS. Therefore, hyperandrogenism and reduced aromatase expression are considered as major factors in PCOS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Instruments & Instrumentation
Letizia Monico, Francesco d'Acapito, Marine Cotte, Koen Janssens, Aldo Romani, Giulia Ricci, Costanza Miliani, Laura Cartechini
Summary: The study of Cr K-edge XANES spectroscopy for surface composition analysis is significant for the long-term conservation of unique paintings from the late 19th-early 20th century, such as Van Gogh's works.
NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS
(2023)
Article
Biochemistry & Molecular Biology
Clement Rouillon, Bruna Eckhardt, Leonie Kollenstart, Fabian Gruss, Alexander E. E. Verkennis, Inge Rondeel, Peter H. L. Krijger, Giulia Ricci, Alva Biran, Theo van Laar, Charlotte M. Delvaux de Fenffe, Georgiana Luppens, Pascal Albanese, Koichi Sato, Richard A. Scheltema, Wouter de Laat, Puck Knipscheer, Nynke H. Dekker, Anja Groth, Francesca Mattiroli
Summary: During cell cycle, CAF-1 plays a crucial role in chromatin replication, and its interaction with the DNA replication machinery remains unknown. The study reveals that the interaction between CAF-1 and replication forks differs between the leading and lagging strand. Biochemical reconstructions demonstrate that DNA and histones promote CAF-1 recruitment to its binding partner PCNA, and two CAF-1 complexes are required for efficient nucleosome assembly. In the context of the replisome, CAF-1 competes with Pol epsilon for PCNA binding on the leading strand, while it does not affect the activity of Pol delta on the lagging strand.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Marika Berardini, Luisa Gesualdi, Caterina Morabito, Francesca Ferranti, Anna Reale, Michele Zampieri, Katsiaryna Karpach, Antonella Tinari, Lucia Bertuccini, Simone Guarnieri, Angela Catizone, Maria A. Mariggio, Giulia Ricci
Summary: The study shows that simulated microgravity exposure can lead to accumulation of reactive oxygen species in TCam-2 cells, along with increased protein and lipid oxidation, and altered mitochondria structure. However, the cells are capable of triggering compensatory mechanisms to overcome the effects of altered gravitational force.
Article
Biochemistry & Molecular Biology
Luisa Gesualdi, Marika Berardini, Bianca Maria Scicchitano, Clotilde Castaldo, Mariano Bizzarri, Antonio Filippini, Anna Riccioli, Chiara Schiraldi, Francesca Ferranti, Domenico Liguoro, Rita Mancini, Giulia Ricci, Angela Catizone
Review
Immunology
Roland S. Liblau, Daniela Latorre, Birgitte R. Kornum, Yves Dauvilliers, Emmanuel J. Mignot
Summary: Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by the loss of certain hypothalamic neurons. It is suspected to have an immune-mediated basis, supported by genetic evidence and increased incidence after vaccination. The search for antigens recognized by pathogenic T cell response in NT1 is ongoing, and animal models provide insights into the roles of autoreactive T cells.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Pediatrics
Nicolo Garancini, Giulia Ricci, Michele Ghezzi, Paola Tommasi, Fiammetta Zunica, Anna Mandelli, Elena Zoia, Enza D'Auria, Gian Vincenzo Zuccotti
Summary: This article reports 4 emblematic cases of invasive Group A Streptococcus (GAS) infections admitted to the Intensive Care Unit (ICU) in a short time span. All patients required intensive care support. These cases emphasize the importance of close monitoring and timely reporting to verify the actual incidence.
ITALIAN JOURNAL OF PEDIATRICS
(2023)