Review
Biochemistry & Molecular Biology
Sanaz Dastghaib, P. Sravan Kumar, Sajjad Aftabi, Gautam Damera, Azadeh Dalvand, Adel Sepanjnia, Mohammad Kiumarsi, Mohamad-Reza Aghanoori, Sukhwinder Singh Sohal, Sudharsana R. Ande, Javad Alizadeh, Pooneh Mokarram, Saeid Ghavami, Pawan Sharma, Amir A. Zeki
Summary: Lung cells are exposed to internal and external stressors, leading to disruption of protein homeostasis and activation of the UPR. Dysregulation of the UPR is associated with disease development and various human conditions. Compounds targeting the UPR pathway show potential for future therapeutic interventions.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Review
Immunology
Wolfgang Vivas, Sebastian Weis
Summary: Pathogens and their toxic byproducts can cause tissue damage in infected hosts, triggering stress responses such as the unfolded protein response (UPR) to limit pathogenesis. However, prolonged or excessive activation of UPR may have detrimental effects including cell death.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Microbiology
Yuki Ishiwata-Kimata, Yukio Kimata
Summary: This article reviews the canonical and up-to-date insights regarding yeast UPR, mainly focusing on the functions and regulation of Ire1 and HAC1.
Review
Biochemistry & Molecular Biology
Noel Verjan Garcia, Kyung U. Hong, Nobuyuki Matoba
Summary: The endoplasmic reticulum (ER) plays a vital role in cell homeostasis and disruptions to its functions can lead to diseases. Dysregulated ER stress and UPR are linked to various human diseases, including inflammatory bowel disease (IBD). A recent study has shown that EPICERTIN can induce a protective UPR in colon epithelial cells, promoting mucosal healing in IBD models.
Article
Biotechnology & Applied Microbiology
Phuong Thi Mai Nguyen, Yuki Ishiwata-Kimata, Yukio Kimata
Summary: The unfolded protein response (UPR) is a cellular response to deal with the accumulation of unfolded proteins in the endoplasmic reticulum (ER). This study demonstrates that constitutive induction of UPR in nonstress conditions leads to growth retardation, which can be partially rescued by weak ER stress. Additionally, the stable expression of ER-localized GFP in UPR-induced cells enhances UPR activity and promotes the production of triglycerides and heterogenous carotenoids. These findings have implications for metabolic engineering and the production of valuable lipidic molecules.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biology
Mateusz Kowalczyk, Edward Kowalczyk, Pawel Kwiatkowski, Lukasz Lopusiewicz, Monika Talarowska, Monika Sienkiewicz
Summary: Despite numerous scientific studies on depression, there is still no clear understanding of the causes and mechanisms of depression development. Recent research has found a strong relationship between depression and endoplasmic reticulum (ER) stress, with continuous activation of stress response pathways in patients. Therefore, recommended drugs should aim at reducing ER stress while alleviating symptoms of depression.ongoing search for drugs that can effectively reduce ER stress and relieve depression symptoms.
Article
Biotechnology & Applied Microbiology
Anja Batel, Mirjana Polovic, Mateo Glumac, Oliver Suman, Stipislav Jadrijevic, Bernarda Lozic, Marija Petrovic, Bobana Samardzija, Nicholas J. Bradshaw, Karlo Skube, Vinko Palada, Mislav Acman, Ivana Marinovic Terzic
Summary: This study reveals the role of the SPRTN gene in hepatocellular carcinoma (HCC) and its association with endoplasmic reticulum (ER) stress, providing new insights into the pathogenesis of HCC.
CANCER GENE THERAPY
(2023)
Review
Plant Sciences
Sofia Reyes-Impellizzeri, Adrian A. Moreno
Summary: This review focuses on the impact of alterations in components of ERQC, ERAD, and UPR on plant responses to abiotic stresses. Evidence shows a clear connection between ERAD and UPR mechanisms, but the connection of ERQC components with these processes or their possible client proteins is lacking. Proteomics approaches are suggested to uncover the identity of these proteins and their connection to ER proteostasis.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Rina Carrillo, David A. Christopher
Summary: A unique biosensor-reporter system was developed to measure UPR activation in plants under stressful environments, demonstrating its utility in Arabidopsis leaf protoplasts for visualization and quantification using confocal microscopy.
PLANT SIGNALING & BEHAVIOR
(2022)
Article
Fisheries
Guang-Xin Liu, Yu Tian, Chang-Hong Cheng, Hong-Ling Ma, Si-Gang Fan, Yi-Qin Deng, Juan Feng, Jian-Jun Jiang, Zhi-Xun Guo
Summary: In this study, a ATF6 gene from the mud crab (Sp-ATF6) was cloned and identified. Sp-ATF6 was widely expressed in different tissues and its expression was induced by hydrogen peroxide and V. parahaemolyticus challenge. Knocking down Sp-ATF6 reduced the expression of antioxidant-related genes and heat shock proteins after V. parahaemolyticus infection.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Article
Plant Sciences
Maria De Benedictis, Antonia Gallo, Danilo Migoni, Paride Papadia, Pietro Roversi, Angelo Santino
Summary: We studied the response of Arabidopsis thaliana to chronic and temporary Cd2+ stress, finding that Cd2+ induces ER stress and unfolded protein response (UPR) through the bZIP60 arm. The UPR activation is concentration- or time-dependent and leads to the activation of ER stress marker genes. Severe Cd2+ stress triggers programmed cell death (PCD) through NAC089 activation. The Atbzip28/bzip60 double mutant shows reduced UPR and PCD, as well as enhanced Cd2+ tolerance, possibly due to increased brassinosteroids signaling.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Review
Endocrinology & Metabolism
Yong Zhou, Yang Jin, Yuan Wang, Ruijin Wu
Summary: Endometriosis is a chronic gynecological disease with an unclear cause. Hypoxia is closely related to the occurrence and development of the disease, with hypoxia-inducible factor-1 alpha playing a key role and the unfolded protein response supplementing cell survival under hypoxic stress.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Cell Biology
Md. Sahab Uddin, Wing Shan Yu, Lee Wei Lim
Summary: Alzheimer's disease is characterized by the accumulation of misfolded proteins due to changes in protein homeostasis, possibly stemming from endoplasmic reticulum stress. The unfolded protein response is a critical signaling cascade that helps reduce misfolded proteins, but age-related changes in ER chaperones and enzymes can disrupt this process. The accumulation of misfolded proteins in AD, caused by sustained cellular stress, leads to neurodegeneration and neuronal death.
AGEING RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Gehan Botrus, Richard M. Miller, Pedro Luiz Serrano Uson Jr, Geoffrey Kannan, Haiyong Han, Daniel D. Von Hoff
Summary: High levels of ER stress and UPR activation are present in pancreatic cancer, leading to adaptive mechanisms and potential apoptosis. This review discusses the mechanisms by which compounds activate the UPR pathways and induce apoptosis, and explores the potential of ER stress inducers for anti-tumor efficacy in pancreatic cancer. A new approach of increasing ER stress and UPR activation to incite apoptotic cell death in pancreatic cancer is hypothesized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Aerospace
Li-Jin Liu, Shuang Li, Xin-Tong Wu, Xiao Yang, Lian-Wen Sun
Summary: This study investigated the role of endoplasmic reticulum stress (ERS) in the altered mechanosensitivity of osteocytes under simulated microgravity (SMG). The results showed that SMG caused an enlargement of the endoplasmic reticulum and an increase in the expression of ERS-related factors, leading to a decrease in the mechanical response of osteocytes. The use of an ERS antagonist, melatonin, was able to counteract these effects.
Article
Mathematical & Computational Biology
Svetlana Cherlin, James M. S. Wason
Summary: The CVRS2 design is a new approach to develop and test the effectiveness of treatment in high-dimensional data. It considers the tradeoff between two outcomes and divides patients into clusters using bivariate risk scores. Through simulated data and a real clinical trial, we demonstrate the reliability and applicability of the CVRS2 design.
Article
Biology
Haiyan Zheng, Thomas Jaki, James M. S. Wason
Summary: This paper develops Bayesian sample size formulae that can incorporate preexperimental information from multiple sources to support both the design and analysis of experiments comparing two groups. The methodology can be applied to various scenarios and provides exact solutions or a search procedure for sample size determination.
Editorial Material
Biology
James M. S. Wason
Article
Health Care Sciences & Services
Michael J. Grayling, James M. S. Wason
Summary: This article describes nine possible point estimators within a common general framework for a two-stage group sequential trial, and compares their performance in five example trial settings. The study finds that two mean adjusted estimators perform best in terms of marginal residual mean square error, considering both conditional and marginal biases.
STATISTICAL METHODS IN MEDICAL RESEARCH
(2023)
Article
Mathematical & Computational Biology
David S. Robertson, James M. S. Wason, Franz Koenig, Martin Posch, Thomas Jaki
Summary: Platform trials evaluate multiple experimental treatments under a single master protocol, with the potential risk of inflating the overall type I error rate due to multiple treatment comparisons and non-pre-specified, time-dependent hypotheses. Online error rate control provides a solution to the problem of multiplicity for platform trials, testing each hypothesis one-by-one over time without knowledge of future tests.
STATISTICS IN MEDICINE
(2023)
Article
Medicine, Research & Experimental
Mark E. McClure, Seerapani Gopaluni, James Wason, Robert B. Henderson, Andre Van Maurik, Caroline C. O. Savage, Charles D. Pusey, Alan D. Salama, Paul A. Lyons, Jacinta Lee, Kim Mynard, David R. Jayne, Rachel B. Jones
Summary: The COMBIVAS study aims to evaluate the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3 AAV. The study includes 30 patients and lasts for 2 years, with a 12-month treatment period followed by a 12-month follow-up period. The primary endpoint is time to PR3 ANCA negativity.
Article
Oncology
Samy Lachkar, Quentin Faur, Florent Marguet, Liana Veresezan, Michael Bubenheim, Mathieu Salaun, Luc Thiberville, Jean-Christophe Sabourin, Florian Guisier, Nicolas Piton
Summary: This study aimed to assess the improvement in diagnostic yield with the combination of EBUS-TBNA and EBUS-IFB compared to EBUS-TBNA alone. The results showed that the diagnostic yield was 94% when EBUS-IFB was combined with EBUS-TBNA, compared to 77% with EBUS-TBNA alone. In terms of histology, the diagnostic yield for nonmalignant conditions was 92% with the combination, compared to 69% with EBUS-TBNA alone.
Article
Medicine, General & Internal
Toshi A. Furukawa, Aran Tajika, Masatsugu Sakata, Yan Luo, Rie Toyomoto, Masaru Horikoshi, Tatsuo Akechi, Norito Kawakami, Takeo Nakayama, Naoki Kondo, Shingo Fukuma, Hisashi Noma, Helen Christensen, Ronald C. Kessler, Pim Cuijpers, James M. S. Wason
Summary: This study aims to develop an iCBT platform that can adapt to the evolving internet technologies and examine the short-term and long-term efficacy of different CBT skills for depression. The study will recruit 3520 participants with subthreshold depression and approximately 1700 participants without subthreshold depression to evaluate the short-term efficacy for reducing depressive symptoms and the long-term efficacy for preventing depression in the total sample.
Article
Mathematical & Computational Biology
Ruqayya A. Azher, James M. S. Wason, Michael J. Grayling
Summary: Randomized controlled trials are the best design for evaluating treatment efficacy, and different randomization procedures can be used to achieve desirable properties. This study compares several allocation procedures for multi-arm trials and finds that stratified block randomization and the stratified block urn design consistently outperform other methods.
STATISTICS IN BIOPHARMACEUTICAL RESEARCH
(2023)
Article
Medicine, General & Internal
Theophile Bigirumurame, Shaun Kuan Wei Hiu, M. Dawn Teare, James M. S. Wason, Andrew Bryant, Matthew Breckons
Summary: This systematic review aims to investigate the practices of studies that apply the target trial emulation framework to evaluate intervention effectiveness using existing observational data. The review will search multiple databases for relevant study reports and protocols and will use a narrative approach to synthesize and report the findings.
Article
Medicine, General & Internal
Miranda Morton, Nina Wilson, Tara Marie Homer, Laura Simms, Alison Steel, Rebecca Maier, James Wason, Laura Ternent, Alaa Abouhajar, Maria Allen, Richard Joyce, Victoria Hildreth, Rachel Lakey, Svetlana Cherlin, Adam Walker, Graham Devereux, James D. Chalmers, Adam T. Hill, Charles Haworth, John R. Hurst, Anthony De Soyza
Summary: This trial aims to investigate whether inhaled dual bronchodilators can reduce the number of exacerbations in bronchiectasis patients. It is a multicentre, double-blind, randomised controlled trial involving 600 adult patients with confirmed bronchiectasis. The primary outcome is the number of exacerbations requiring antibiotic treatment during a 12-month period.
Review
Oncology
Benjamin Bottet, Nicolas Piton, Jean Selim, Matthieu Sarsam, Florian Guisier, Jean-Marc Baste
Summary: Lung cancer is a heterogeneous disease that presents significant challenges in diagnosis and treatment. Recent advances in surgery, perioperative management, and targeted therapy have revolutionized the treatment landscape for this disease, offering new hope for patients. This review aims to provide a comprehensive understanding of the latest surgical approaches in lung cancer and emphasizes the importance of integrating these modalities within a patient-centered and personalized treatment pathway.