Article
Biochemistry & Molecular Biology
Jing Liu, Pingyang Ke, Haokun Guo, Juan Gu, Yan Liu, Xin Tian, Xuefeng Wang, Fei Xiao
Summary: A study found that Toll-like receptor 7 (TLR7) is activated in the early stage of epileptogenesis and affects epileptogenesis by regulating autophagy and inhibitory synaptic transmission. Activation of TLR7 induces autophagy and decreases the expression of KIF5A, which in turn influences abnormal GABA(A)R-mediated postsynaptic transmission. The results indicate that TLR7 is an important factor in regulating epileptogenesis and may serve as a potential therapeutic target for epilepsy.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Sung-Wook Hong, Peter D. Krueger, Kevin C. Osum, Thamotharampillai Dileepan, Adam Herman, Daniel L. Mueller, Marc K. Jenkins
Summary: Exposure to food antigens leads to the formation of various noncanonical T helper cell subsets by naive CD4(+) T cells, which lack inflammatory functions but have the potential to produce regulatory T cells that may suppress gut pathology.
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
Pharmacology & Pharmacy
Chunli Huang, Changsheng Dong, Yanan Zhu, Yang Yu, Huizi Jin, Yan Zhang
Summary: Duhaldea pterocaula, also known as Inula pterocaula, is a folk medicine of the Yi nationality in China with anti-inflammatory and analgesic properties. The study found that the ethyl acetate fraction of I. pterocaula had potent analgesic effects, potentially mediated through the GABA(A)R pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Katarzyna Terejko, Michal A. Michalowski, Anna Dominik, Anna Andrzejczak, Jerzy W. Mozrzymas
Summary: Recent studies have shown that the activation of pLGICs is associated with coordinated subunit twisting in the membrane plane, indicating a crucial role of intersubunit interactions in receptor activation, especially in preactivation and opening processes. The underlying mechanisms of this intersubunit cross-talk outside the top-down pathway remain largely unknown.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Gal Ofir, Ehud Herbst, Maya Baroz, Daniel Cohen, Adi Millman, Shany Doron, Nitzan Tal, Daniel B. A. Malheiro, Sergey Malitsky, Gil Amitai, Rotem Sorek
Summary: The TIR domain plays a crucial role in animal and plant immune systems, triggering cell death and participating in the bacterial antiviral defence system Thoeris. Research findings suggest that TIR-domain proteins in bacteria recognize infection and produce signalling molecules to execute cell death, similar to the roles of these proteins in plants.
Article
Biochemistry & Molecular Biology
Xiaofei She, Shijun Shen, Guang Chen, Yaqun Gao, Junxian Ma, Yaohui Gao, Yingdi Liu, Guoli Gao, Yan Zhao, Chunyan Wang, Cizhong Jiang, Ping Wang, Huanlong Qin, Hua Gao
Summary: Brain metastasis, most commonly originating from lung cancer, is associated with high morbidity and mortality. A study using genome-wide CRISPR-Cas9 screening found that loss of IFITM1 promotes the colonization of human lung cancer cells in the brain. Elevated IFITM1 expression in brain metastatic cells activates microglia and enhances the cytolytic activity of CD8(+) T cells, leading to the elimination of cancer cells. Clinical trials showed that the response to immune checkpoint blockade therapy is correlated with IFITM1 expression, and combining IFITM1 expression with PD-1 blockade can effectively suppress brain metastasis.
Article
Neurosciences
Shuang Zeng, Ruilou Zhu, Yangyang Wang, Yitian Yang, Ningning Li, Ningning Fu, Mingyang Sun, Jiaqiang Zhang
Summary: The study found that sevoflurane anesthesia in neonatal mice caused cognitive impairment, increased the expression of Gabrb3 and Cav1.2 in hippocampal neurons, elevated calcium ion concentration, inflammation, neuron apoptosis, reduced neuron proliferation in the DG area, and decreased dendritic spine density. Inhibition of Gabrb3 and Cav1.2 alleviated cognitive impairment and reduced neurotoxicity.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Na Wang, Jingjing Lian, Yanqing Cao, Alai Muheyati, Shanshan Yuan, Yujie Ma, Shuzhuo Zhang, Gang Yu, Ruibin Su
Summary: Benzodiazepines produce various pharmacological effects by positively modulating GABA(A) receptors. This study found that different concentrations of drugs have different effects on different GABA(A) receptors and vary in sensitivity to flumazenil. The results also support the existence of non-classical benzodiazepine binding sites on certain GABA(A) receptor subtypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Plant Sciences
Yihan Gong, Lei Tian, Ilias Kontos, Josh Li, Xin Li
Summary: Plant NLRs are important immune receptors for pathogen recognition and signal transduction. Helper NLRs are required by both membrane-localized PRRs and sNLRs for immune signaling. Recent studies have revealed the structural and biochemical mechanisms of helper NLRs in immune signaling, such as the formation of oligomeric resistosomes and membrane calcium channels. The research on plant helper NLRs provides valuable insights into the immune response mechanisms in plants.
CURRENT OPINION IN PLANT BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Haram R. Kim, Lakshmi Rajagopal, Herbert Y. Meltzer, Marco Martina
Summary: This study suggests that altering the polarity of GABA(A) currents in the ILC can improve cognitive performance in a mouse model of schizophrenia, indicating that bumetanide may have the potential to treat or prevent CIAS.
Article
Multidisciplinary Sciences
Gabriele Ruffolo, Veronica Alfano, Alessia Romagnolo, Till Zimmer, James D. Mills, Pierangelo Cifelli, Alessandro Gaeta, Alessandra Morano, Jasper Anink, Angelika Muhlebner, Annamaria Vezzani, Eleonora Aronica, Eleonora Palma
Summary: This study found that the key anti-inflammatory cytokine IL-10 can significantly enhance GABAergic neurotransmission in Gangliogliomas (GGs) brain tumors, while the pro-inflammatory cytokine IL-1 beta reduces GABA current amplitude. These results suggest that in epileptogenic tissue, pro-inflammatory mechanisms of hyperexcitability prevail over key anti-inflammatory pathways.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Mengmeng Chang, Kirin D. Gada, Bojjibabu Chidipi, Athanasios Tsalatsanis, Justin Gibbons, Elizabeth Remily-Wood, Diomedes E. Logothetis, Jenna Oberstaller, Sami F. Noujaim
Summary: This study found that in the aging heart, IKACh is constitutively active in a PKCE-dependent manner, leading to the occurrence of AF. Knocking out PKCE can eliminate the effects of aging on AF and prevent the activation of IKACh.
Review
Immunology
Yves Laumonnier, Rabia Uelkue Korkmaz, Alicja A. Nowacka, Joerg Koehl
Summary: Allergic conditions involve the activation of the complement system and release of bioactive mediators, which regulate the immune response to allergens. The immune sensors and regulator proteins of the complement cascade also impact the development of allergies. This article provides an update on the roles of complement in allergic diseases, with a focus on the anaphylatoxins C3a and C5a and their receptors.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Mari T. Iwasawa, Hideaki Miyachi, Seiichiro Wakabayashi, Takashi Sugihira, Reika Aoyama, Seitaro Nakagawa, Yuki Katayama, Mitsutoshi Yoneyama, Hiromitsu Hara, Yoichiro Iwakura, Masanori Matsumoto, Naohiro Inohara, Hanako Koguchi-Yoshioka, Manabu Fujimoto, Gabriel Nunez, Hiroyuki Matsue, Yuumi Nakamura, Shinobu Saijo
Summary: This study found that IL-17A and IL-17F play critical and redundant roles in host defense against C. albicans in the epidermis through their production by ILC3s. Furthermore, clearance of C. albicans in the epidermis is independent of innate immune receptors or these receptors act redundantly in fungal recognition and clearance.
INTERNATIONAL IMMUNOLOGY
(2022)
Article
Nutrition & Dietetics
Camille Martin-Gallausiaux, Ludovica Marinelli, Herve M. Blottiere, Pierre Larraufie, Nicolas Lapaque
Summary: This article discusses the mechanisms and impact of short-chain fatty acids (SCFA) on gut functions, host immunity, and human health. SCFA, derived from bacterial fermentation of dietary fibers, serve as important fuels for intestinal epithelial cells and modulate various functions to impact intestinal homeostasis.
PROCEEDINGS OF THE NUTRITION SOCIETY
(2021)
Article
Biophysics
J. Loke, M. Labopin, C. Craddock, D. Niederwieser, J. Cornelissen, B. Afansayev, P. Jindra, J. Maertens, D. Blaise, K. Boriskina, M. Gramatzki, A. Ganser, B. Savani, M. Mohty, A. Nagler
Summary: A study of 937 AML patients undergoing transplantation from a mismatched unrelated donor found that patient age, adverse karyotype, and CMV seropositivity were correlated with decreased LFS and OS. There was no significant difference in LFS or OS between patients transplanted from donors mismatched at different HLA loci, but HLA-A mismatched transplants were associated with higher rates of acute GVHD and NRM. Patient CMV seropositivity was linked to increased NRM and acute GVHD, as well as reduced LFS and OS.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Charles Craddock, Aimee Jackson, Justin Loke, Shamyla Siddique, Andrea Hodgkinson, John Mason, Georgia Andrew, Sandeep Nagra, Ram Malladi, Andrew Peniket, Maria Gilleece, Rahuman Salim, Eleni Tholouli, Victoria Potter, Charles Crawley, Keith Wheatley, Rachel Protheroe, Paresh Vyas, Ann Hunter, Anne Parker, Keith Wilson, Jiri Pavlu, Jenny Byrne, Richard Dillon, Naeem Khan, Nicholas McCarthy, Sylvie D. Freeman
Summary: The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes for adults undergoing transplantation for high-risk AML or MDS, regardless of pretransplant MRD status. Pretransplant detectable MRD was associated with disease relapse, but acquisition of full donor T-cell chimerism improved overall survival.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Immunology
Justin Loke, Richard Buka, Charles Craddock
Summary: While most AML patients achieve complete remission with intensive chemotherapy, many face a risk of relapse if treated with chemotherapy alone. Allogeneic stem cell transplant has become a key treatment strategy for AML patients, especially for those in first complete remission and advanced stages. Despite a decrease in transplant-related mortality, there remains a need to address the risk of disease relapse.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Justin Loke, Hrushikesh Vyas, Charles Craddock
Summary: AML is the most common indication for allo-SCT worldwide, with advancements in risk stratification, donor availability, and conditioning regimens expanding transplant access for high risk patients. Disease relapse remains the top cause of transplant failure, highlighting the need for novel strategies to reduce recurrence risk.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Hematology
Justin Loke, Peter N. Cockerill
Summary: The study demonstrates that monocytic cells from CMML patients are vulnerable to synergistic inhibition of the antiapoptotic protein MCL-1 and the RAS/MAPK signaling pathway kinases MEK1 and MEK2.
Letter
Hematology
Dominic O'Connor, Justin Loke, Malcolm Brown, Simon J. Stanworth, Annie Young, Gillian Prue
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Justin Loke, Marlen Metzner, Rebecca Boucher, Aimee Jackson, Louise Hopkins, Jiri Pavlu, Eleni Tholouli, Mark Drummond, Andy Peniket, Rebecca Bishop, Sonia Fox, Paresh Vyas, Charles Craddock
Summary: The ROMAZA trial established the maximum tolerated dose of combined ROM/AZA therapy for AML patients, with ROM 12 mg/m(2) on Days 8 and 15, and AZA 75 mg/m(2) administered for 7/28 day cycle. Among patients treated at the maximum tolerated dose, 23.7% were classified as responders by Cycle 6. Correlative next-generation sequencing studies provided important insights into therapy resistance.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Neurosciences
Zehra Esra Ilhan, Vincent Brochard, Nicolas Lapaque, Stephane Auvin, Patricia Lepage
Summary: Anti-seizure medications can affect the gut microbiota and have different impacts on the growth of gut bacterial strains. The toxicity of medication ingredients varies and can also affect gut epithelial cells. Gut microbial metabolites may play a role in mediating the interaction between medications and epithelial cells.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Immunology
Xufei Zhang, Magali Monnoye, Mahendra Mariadassou, Fabienne Beguet-Crespel, Nicolas Lapaque, Christine Heberden, Veronique Douard
Summary: The study revealed different impacts of fructose and glucose intake on mice, with glucose leading to increased adiposity, glucose intolerance, and intestinal permeability, while fructose resulted in elevated IL6 levels. The research also identified the potential roles of microbiota composition and inflammatory factors in gut barrier function and inflammation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Justin Loke, Myriam Labopin, Charles Craddock, Jan J. Cornelissen, Helene Labussiere-Wallet, Eva Maria Wagner-Drouet, Gwendolyn Van Gorkom, Nicolaas P. M. Schaap, Nicolaus M. Kroger, Joan Hendrik Veelken, Montserrat Rovira, Anne Lise Menard, Gesine Bug, Ali Bazarbachi, Sebastian Giebel, Eolia Brissot, Arnon Nagler, Jordi Esteve, Mohamad Mohty
Summary: This study found that TP53 mutations are associated with unfavorable outcomes in AML patients with intermediate or adverse-risk cytogenetics. However, in patients without co-occurring 17p- and/or complex karyotype mutations, the adverse effect of TP53 mutations on allogeneic stem cell transplantation is not evident.
Article
Gastroenterology & Hepatology
Camille Martin-Gallausiaux, Diego Garcia-Weber, Amandine Lashermes, Pierre Larraufie, Ludovica Marinelli, Veronica Teixeira, Alice Rolland, Fabienne Beguet-Crespel, Vincent Brochard, Timothe Quatremare, Alexandre Jamet, Joel Dore, Scott D. Gray-Owen, Herve M. Blottiere, Cecile Arrieumerlou, Nicolas Lapaque
Summary: The gut microbiota has an impact on the health of the host through interactions with intestinal epithelial cells. It has been found that the commensal bacterium A. muciniphila promotes intestinal homeostasis by activating the ALPK1/TIFA/TRAF6 axis, a pathway associated with innate immunity.
Article
Hematology
Justin Loke, Vinit Upasani, Charlotte Gaskell, Sonia Fox, Rachel Fletcher, Catherine Thomas, Louise Hopkins, Anita Kumari, Tina Tang, Emily Yafai, Rebecca Boucher, Victoria Homer, Arpad Toth, Y. L. Tracey Chan, Katie Randall, Tom Rider, Jenny O'Nions, Victoria Drew, Arvind Pillai, Moez Dungarwalla, Duncan Murray, Anjum Khan, Farooq Wandroo, Sally Moore, Pramila Krishnamurthy, Ya-Wen Jessica Huang, Steve Knapper, Jenny Byrne, Rui Zhao, Charles Craddock, Helen Parry, Paul Moss, Simon J. Stanworth, David M. Lowe
Summary: Limited data exist on the efficacy of COVID-19 vaccination in patients with AML/MDS-EB2. A prospective study found detectable antibodies against SARS-COV-2 spike antigen in all post-vaccine samples. T-cell reactivity to SARS-COV-2 spike protein was only seen in a subset of patients, and disease response and age were predictors of poor T-cell response.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Justin Loke, Nicholas McCarthy, Aimee Jackson, Shamyla Siddique, Andrea Hodgkinson, John Mason, Charles Crawley, Maria Gilleece, Andrew Peniket, Rachel Protheroe, Rahuman Salim, Eleni Tholouli, Keith Wilson, Georgia Andrew, Richard Dillon, Naeem Khan, Victoria Potter, Pramila Krishnamurthy, Charles Craddock, Sylvie Freeman
Summary: This study reports the prognostic impact of biomarkers including MRD, T-cell chimerism, and blast HLA-DR expression in AML/MDS patients receiving allogeneic stem-cell transplant. MRD positivity is associated with reduced overall survival, while MRD is infrequent and does not affect the outcome in patients with full donor T-cell chimerism.
Meeting Abstract
Biophysics
Justin Loke, Myriam Labopin, Charles Craddock, Jan J. Cornelissen, Helene Labussiere-Wallet, Eva Maria Wagner-Drouet, Gwendolyn Van Gorkom, Nicolaas Schaap, Nicolaus Kroeger, Joan Hendrik Veelken, Montserrat Rovira, Herve Tilly, Hans Martin, Gesine Bug, Ali Bazarbachi, Sebastian Giebel, Eolia Brissot, Arnon Nagler, Jordi Esteve, Mohamad Mohty
BONE MARROW TRANSPLANTATION
(2021)