Review
Pathology
Sun-Ji Park, Chuang Li, Ying Maggie Chen
Summary: Maintaining Ca2+ homeostasis is crucial for cellular function and survival, with the endoplasmic reticulum acting as the major intracellular Ca2+ store. Dysregulation of ER Ca2+ homeostasis is associated with various diseases, particularly in kidney diseases, highlighting the importance of ER Ca2+ channels, pumps, and binding proteins. Despite advancements in understanding, treatment for ER Ca2+ imbalance in kidney diseases remains elusive.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lukas Kuester, Themistoklis Paraschiakos, Kader Ebru Karakurt, Udo Schumacher, Bjoern-Philipp Diercks, Sabine Windhorst
Summary: The up-regulation of ITPKA in lung cancer cells is associated with increased migration and invasion, and its actin bundling activity is the main factor controlling this effect.
BIOSCIENCE REPORTS
(2023)
Article
Cell Biology
Ana M. Rossi, Andrew M. Riley, Genevieve Dupont, Taufiq Rahman, Barry V. L. Potter, Colin W. Taylor
Summary: Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are intracellular Ca2+ channels linking extracellular stimuli to Ca2+ signals. Research shows that quantal responses to low IP3 concentrations do not require heterogeneous Ca2+ stores, and IP(3)Rs exhibit incremental responses to IP3 stimulation. This suggests that Ca2+ signals evoked by IP3 pulses arise from rapid activation and inactivation of a small fraction of IP(3)Rs.
Article
Computer Science, Artificial Intelligence
Randall Clark, Lawson Fuller, Jason A. Platt, Henry D. I. Abarbanel
Summary: This article introduces how to use methods from nonlinear dynamics and interpolation techniques from applied mathematics to construct discrete time dynamical rules that forecast observed neuron properties accurately, which is crucial for the development of neural network models and biological networks.
NEURAL COMPUTATION
(2022)
Article
Biochemistry & Molecular Biology
Laura Marongiu, Francesca Mingozzi, Clara Cigni, Roberta Marzi, Marco Di Gioia, Massimiliano Garre, Dario Parazzoli, Laura Sironi, Maddalena Collini, Reiko Sakaguchi, Takashi Morii, Mariacristina Crosti, Monica Moro, Stephane Schurmans, Tiziano Catelani, Rany Rotem, Miriam Colombo, Stephen Shears, Davide Prosperi, Ivan Zanoni, Francesca Granucci
Summary: Recognition of LPS by DCs involves the receptor complex CD14 and TLR4, and subsequent Ca2+ mobilization and NFAT activation require IP3R3 and ITPKB. Targeting ITPKB may offer a promising approach for anti-inflammatory therapies aimed at inhibiting specific DC functions.
Article
Multidisciplinary Sciences
Nagendra Babu Thillaiappan, Holly A. Smith, Peace Atakpa-Adaji, Colin W. Taylor
Summary: The study demonstrates that the KRas-induced KRAP protein tethers a subset of IP3 receptors to actin, enabling them to evoke calcium signals. Loss of KRAP results in the disappearance of Ca2+ puffs and a global response to increased cytosolic Ca2+ concentration from more intense stimulation.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Arthur Bassot, Junsheng Chen, Kei Takahashi-Yamashiro, Megan C. Yap, Christine Silvia Gibhardt, Giang N. T. Le, Saaya Hario, Yusuke Nasu, Jack Moore, Tomas Gutierrez, Lucas Mina, Heather Mast, Audric Moses, Rakesh Bhat, Klaus Ballanyi, Helene Lemieux, Roberto Sitia, Ester Zito, Ivan Bogeski, Robert E. Campbell, Thomas Simmen
Summary: Endoplasmic reticulum (ER) homeostasis relies on molecular regulators, such as calnexin and NOX4, to maintain mitochondrial metabolism and ER-mitochondria contacts. During ER stress induction, the PERK-ERO1a complex interacts and promotes oxidation of MERC proteins, controlling mitochondrial dynamics and improving ER-mitochondria Ca2+ flux for bioenergetics maintenance. This complex plays a crucial role in quick metabolic adaptation to ER stress.
Article
Neurosciences
Astrid Kollewe, Yvonne Schwarz, Katharina Oleinikov, Ahsan Raza, Alexander Haupt, Philipp Wartenberg, Amanda Wyatt, Ulrich Boehm, Fabien Ectors, Wolfgang Bildl, Gerd Zolles, Uwe Schulte, Dieter Bruns, Veit Flockerzi, Bernd Fakler
Summary: This study reveals the macro-molecular complex structure of TRPC channels in the mammalian brain and elucidates their subunit composition and activation mechanism.
Article
Multidisciplinary Sciences
Iqbal Dulloo, Peace Atakpa-Adaji, Yi-Chun Yeh, Clemence Levet, Sonia Muliyil, Fangfang Lu, Colin W. Taylor, Matthew Freeman
Summary: This study reveals that iRhom pseudoproteases regulate cell death by modulating the inhibitory interaction between BCL-2 and IP3 receptors. Loss of iRhoms leads to resistance to ER stress-induced apoptosis. This finding extends the potential pathological significance of iRhoms to diseases dependent on protein misfolding and aggregation.
NATURE COMMUNICATIONS
(2022)
Article
Food Science & Technology
Xueqin Feng, Tiantian Yu, Yumeng Zhang, Lijuan Li, Miaomiao Qu, Jishui Wang, Fangxiang Dong, Lihua Zhang, Fengge Wang, Fanyong Zhang, Xiuwen Zhou, Zhice Xu, Dongmei Man
Summary: The study shows that prenatal high sucrose diet can lead to vascular dysfunction in fetal offspring by enhancing AT1 receptor, LTCC function, and IP3Rs-associated calcium channels.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Lukas Kuester, Themistoklis Paraschiakos, Kader Ebru Karakurt, Udo Schumacher, Bjoern-Philipp Diercks, Sabine Windhorst
Summary: Expression of ITPKA is up-regulated in many tumor types and is associated with bad prognosis in lung cancer cells. It has been shown that high levels of ITPKA increase migration and invasion of lung cancer cell lines. The study demonstrates that the actin bundling activity of ITPKA controls migration and invasion under basal conditions, while the Ins(1,4,5)P-3-kinase activity slightly enhances this effect in the presence of ATP.
BIOSCIENCE REPORTS
(2023)
Article
Physics, Fluids & Plasmas
Irina Bashkirtseva, Lev Ryashko
Summary: The stochastic excitability of spiking oscillatory regimes in calcium kinetics is investigated using the Li-Rinzel conceptual model. The probabilistic mechanisms of noise-induced generation of large-amplitude oscillations in parametric zones are studied numerically and analytically. The phenomenon of coherence resonance is discussed, and a parametric statistical description of interspike intervals is applied. The role of confidence ellipses and separatrices in determining sub- and supercritical regions is demonstrated.
Article
Biophysics
Victor Nicolai Friedhoff, Benjamin Lindner, Martin Falcke
Summary: This article investigates the randomness and properties of Ca2+ signaling in cells. The researchers found that the generation of Ca2+ spikes follows certain patterns and can be described as a process from one state to another. They proposed a theoretical model to explain the differences in spike behavior between different cell types and stimulating agonists, as well as the variability observed in experiments.
BIOPHYSICAL JOURNAL
(2023)
Article
Multidisciplinary Sciences
Valerio Farfariello, Dmitri Gordienko, Lina Mesilmany, Yasmine Touil, Emmanuelle Germain, Ingrid Fliniaux, Emilie Desruelles, Dimitra Gkika, Morad Roudbaraki, George Shapovalov, Lucile Noyer, Mathilde Lebas, Laurent Allart, Nathalie Zienthal-Gelus, Oksana Iamshanova, Franck Bonardi, Martin Figeac, William Laine, Jerome Kluza, Philippe Marchetti, Bruno Quesnel, Daniel Metzger, David Bernard, Jan B. Parys, Loic Lemonnier, Natalia Prevarskaya
Summary: This study reveals the mechanism of how alterations in mitochondrial function and calcium signaling contribute to cellular senescence and tumor growth. The downregulation of TRPC3 protein in senescent fibroblasts leads to increased mitochondrial calcium load and oxidative phosphorylation, promoting cellular senescence. The downregulation of TRPC3 in stromal cells also affects secretome and tumor progression, highlighting its importance in cancer development.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Yaozhi Zhang, Yang Wu, Minjie Zhang, Zixian Li, Bin Liu, Huafeng Liu, Junfeng Hao, Xiaoyu Li
Summary: Organelles are functional areas in eukaryotic cells that perform vital processes for life, and they interact with each other for coordinated functions. Disorders in organelle networks are often implicated in various diseases. The endoplasmic reticulum and mitochondria are crucial organelles in eukaryotic cells, responsible for material synthesis and oxidative metabolism. Understanding the mode and mechanism of organelle crosstalk remains a challenge, as well as the intricate association between organelle dyshomeostasis and human diseases. This paper provides a systematic summary of the latest research on the synergistic mechanism between the endoplasmic reticulum and mitochondria, their crosstalk with other organelles, and highlights the potential application of maintaining organelle homeostasis as a strategy for disease prevention and treatment.
CELL DEATH DISCOVERY
(2023)
Article
Ophthalmology
Fan Yang, Isami Hayashi, Shinri Sato, Yumiko Saijo-Ban, Mio Yamane, Masaki Fukui, Eisuke Shimizu, Jingliang He, Shinsuke Shibata, Shin Mukai, Kazuki Asai, Mamoru Ogawa, Yuqing Lan, Qingyan Zeng, Akito Hirakata, Kazuo Tsubota, Yoko Ogawa
Summary: The study revealed that sclerodermatous chronic graft-versus-host disease (cGVHD) can lead to pathological changes in blood vessels and meibomian glands (MGs) in the eyelids, including endothelial injury and activation, neovascularization, fibrotic changes, immune cell infiltration, and necrosis and apoptosis of MG basal cells.
Article
Rheumatology
Daniel Aletaha, Andreas Kerschbaumer, Kastriot Kastrati, Christian Dejaco, Maxime Dougados, Iain B. McInnes, Naveed Sattar, Tanja A. Stamm, Tsutomu Takeuchi, Michael Trauner, Desiree van der Heijde, Marieke Voshaar, Kevin L. Winthrop, Angelo Ravelli, Neil Betteridge, Gerd-Ruediger R. Burmester, Johannes W. J. Bijlsma, Vivian Bykerk, Roberto Caporali, Ernest H. Choy, Catalin Codreanu, Bernard Combe, Mary K. Crow, Maarten de Wit, Paul Emery, Roy M. Fleischmann, Cem Gabay, Merete Lund Hetland, Kimme L. Hyrich, Annamaria Iagnocco, John D. Isaacs, Joel M. Kremer, Xavier Mariette, Peter Merkel, Eduardo F. Mysler, Peter Nash, Michael T. Nurmohamed, Karel Pavelka, Gyula Poor, Andrea Rubbert-Roth, Hendrik Schulze-Koops, Anja Strangfeld, Yoshiya Tanaka, Josef S. Smolen
Summary: This paper is an updated consensus document on the medical use of IL-6 pathway inhibition in the treatment of inflammatory diseases. The document provides comprehensive consensus statements based on systematic literature research and expert opinion, covering various aspects of IL-6 pathway inhibitors, including dosing, indications, and clinical considerations.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Yoshiya Tanaka, Masafumi Kawanishi, Megumi Nakanishi, Hironori Yamasaki, Tsutomu Takeuchi
Summary: Subcutaneous ozoralizumab treatment for 52 weeks demonstrated significant therapeutic effects and acceptable tolerability in patients with active rheumatoid arthritis.
MODERN RHEUMATOLOGY
(2023)
Article
Ophthalmology
Yoko Ogawa, Reza Dana, Stella Kim, Sandeep Jain, Mark I. Rosenblatt, Victor L. Perez, Janine A. Clayton, Monica Alves, Eduardo Melani Rocha, Francisco Amparo, Kyoung Yul Seo, Yan Wang, Joanne Shen, Joo Youn Oh, Murugesan Vanathi, Sridevi Nair, Kyung-Sun Na, Anjo Riemens, Kimberly Sippel, Matias Soifer, Shudan Wang, Marilia Trindade, Mee Kum Kim, Chang Ho Yoon, Ryuichiro Yagi, Ryo Hiratsuka, Mamoru Ogawa, Eisuke Shimizu, Yasunori Sato, Stephen Pflugfelder, Kazuo Tsubota
Summary: The study validates the consistency between ICCGVHD and NIH2014 in the diagnosis of chronic ocular GVHD. ICCGVHD score =6 can be useful in diagnosing ocular GVHD with or without systemic GVHD for clinical research.
Review
Rheumatology
Sytske Anne Bergstra, Alexandre Sepriano, Andreas Kerschbaumer, Desiree van der Heijde, Roberto Caporali, Christopher John Edwards, Patrick Verschueren, Savia de Souza, Janet E. Pope, Tsutomu Takeuchi, Kimme L. Hyrich, Kevin L. Winthrop, Daniel Aletaha, Tanja A. Stamm, Jan W. Schoones, Josef S. Smolen, Robert B. M. Landewe
Summary: This systematic literature review examines the efficacy, duration of use, and safety of glucocorticoids (GCs) in the management of rheumatoid arthritis (RA). The study confirms the effectiveness of GCs in treating RA, with most patients able to stop GCs within 12-24 months. However, the use of GCs also carries well-known safety risks, including osteoporotic fractures, serious infections, diabetes, and mortality.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Tsutomu Takeuchi, Sakae Tanaka, Mitsuru Murata, Yoshiya Tanaka
Summary: This study aimed to evaluate the efficacy and safety of TAS5315 in Japanese patients with refractory rheumatoid arthritis. The results showed numerical differences in disease activity improvement rates between the TAS5315 group and the placebo group at week 12, but the primary endpoint was not achieved. However, TAS5315 demonstrated advantages in disease activity and biomarker improvement, as well as higher risk of bleeding events within 36 weeks. Therefore, a risk-benefit analysis of TAS5315 should be considered.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Yoshiya Tanaka, Tsutomu Takeuchi, Derek Haaland, Stephen Hall, Nevsun Inanc, Zhanguo Li, Ricardo M. M. Xavier, Carlos Cara, Nicola Tilt, Peter C. C. Taylor
Summary: This study assessed the efficacy of Certolizumab pegol (CZP) in patients with early and established rheumatoid arthritis (RA) and found that it was effective in reducing symptoms in patients with different rheumatoid factors (RF) levels. CZP may be considered as a treatment option for RA.
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Peter C. Taylor, Michael E. Weinblatt, Iain B. McInnes, Tatsuya Atsumi, Vibeke Strand, Tsutomu Takeuchi, Marguerite Bracher, David Brooks, John Davies, Christopher Goode, Anubha Gupta, Sumanta Mukherjee, Ciara O'Shea, Didier Saurigny, Lorrie A. Schifano, Celia Shelton, Julia E. Smith, Millie Wang, Reena Wang, Sarah Watts, Roy M. Fleischmann
Summary: This study investigated the efficacy and safety of otilimab in patients with active rheumatoid arthritis. The results showed that otilimab did not achieve the primary endpoint of ACR20 and did not demonstrate non-inferiority to sarilumab in this patient population.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Satoshi Takanashi, Yasushi Kondo, Shuntaro Saito, Jun Kikuchi, Hironari Hanaoka, Tsutomu Takeuchi, Yuko Kaneko
Summary: Rituximab is an effective treatment option for patients with lymphoproliferative disorder and rheumatoid vasculitis, showing significant improvements in disease activity scores and reduction in prednisolone dosage, with a good safety profile.
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2023)
Article
Pharmacology & Pharmacy
Tsutomu Takeuchi, Yukihiro Chino, Yoko Mano, Masafumi Kawanishi, Yuri Sato, Saeko Uchida, Yoshiya Tanaka
Summary: A population pharmacokinetic (PK) model was developed to assess the effects of potential PK covariates on the PK of ozoralizumab. The model adequately described the PK of ozoralizumab in Japanese patients with rheumatoid arthritis, and body weight was found to have the greatest impact on its PK.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Rheumatology
Tsutomu Takeuchi, Megumi Nakanishi, Masafumi Kawanishi, Hironori Yamasaki, Yoshiya Tanaka
Summary: This article evaluates the efficacy and safety of extending the dosing interval of ozoralizumab from every 4 weeks to every 8 weeks in patients with rheumatoid arthritis (RA). The results indicate that extending the dosing interval is effective and well tolerated in patients maintaining a disease activity score below 3.2.
MODERN RHEUMATOLOGY
(2023)
Editorial Material
Rheumatology
Marc Feldmann, Ravinder N. Maini, Enrique R. Soriano, Vibeke Strand, Tsutomu Takeuchi
Summary: In this Viewpoint article, five rheumatology researchers discuss how biologic therapy has transformed clinical practice and reflect on their own experiences, past and current challenges, and the future prospects of biologic drugs.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Rheumatology
Tsutomu Takeuchi, Yukihiro Chino, Masafumi Kawanishi, Megumi Nakanishi, Hirotaka Watase, Yoko Mano, Yuri Sato, Saeko Uchida, Yoshiya Tanaka
Summary: This study aimed to analyze the pharmacokinetics (PK) of Ozoralizumab (OZR) and its correlation with clinical efficacy in rheumatoid arthritis (RA) patients. The results showed that the maximum plasma concentration (C-max) of OZR was reached in 6 days, with a half-life of 18 days. The exposure of OZR correlated negatively with patient body weight and was not significantly affected by other patient baseline characteristics. The efficacy of OZR was sustained independent of trough concentration when administered subcutaneously at a dose of 30 mg every 4 weeks for 52 weeks.
ARTHRITIS RESEARCH & THERAPY
(2023)
Review
Immunology
Tsutomu Takeuchi
Summary: This review provides an overview of cytokines and cytokine receptors approved in immune-mediated inflammatory diseases (IMID) and discusses their role, treatment modalities, and updated molecular information in each disease, with rheumatoid arthritis as a role model.
INFLAMMATION AND REGENERATION
(2022)
Article
Rheumatology
Tsutomu Takeuchi, Masafumi Kawanishi, Megumi Nakanishi, Hironori Yamasaki, Yoshiya Tanaka
Summary: This study assessed the efficacy and safety of ozoralizumab plus methotrexate in patients with active rheumatoid arthritis. The results showed that ozoralizumab significantly reduced the signs and symptoms of RA compared to placebo, with acceptable tolerability.
ARTHRITIS & RHEUMATOLOGY
(2022)
