Review
Psychiatry
Derek Hong, Lilia M. Iakoucheva
Summary: Significant progress has been made in identifying risk genes for Autism Spectrum Disorder (ASD) in the past decade, specifically loss-of-function (LoF) mutations. However, there has been a lack of clinical advancements in ASD therapeutics. To address this, various therapeutic techniques are being developed to rescue the effects of these mutations at the DNA, mRNA, and protein levels, including CRISPR activation (CRISPRa), gene replacement, antisense oligonucleotides (ASOs), and small-molecule drugs. Delivery methods that effectively cross the blood-brain barrier (BBB) are crucial for successful ASD therapeutics.
TRANSLATIONAL PSYCHIATRY
(2023)
Review
Pharmacology & Pharmacy
Stefano A. Serapian, Carlos Sanchez-Martin, Elisabetta Moroni, Andrea Rasola, Giorgio Colombo
Summary: TRAP1, the mitochondrial isoform of heat shock protein (Hsp)90 chaperones, plays a crucial role in regulating metabolism and organelle homeostasis in various pathological states. Developing TRAP1-directed strategies, including lead modification with mitochondria delivery groups and computational discovery of allosteric sites and ligands, opens up unique opportunities in addressing fundamental questions on its biology and unveiling new therapeutic approaches. Predicting the activities of TRAP1-selective allosteric ligands and optimizing target engagement to avoid side effects are crucial in this endeavor.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Review
Biotechnology & Applied Microbiology
Giampaolo Calissi, Eric W. -F. Lam, Wolfgang Link
Summary: FOXO proteins are transcription factors that are involved in regulating stress responses to maintain cellular homeostasis. Dysregulation of FOXO protein functions contributes to cardiovascular disease, cancer, diabetes, and neurological diseases. This review summarizes the biology of FOXO proteins, their roles in disease and longevity, and discusses pharmacological approaches to develop FOXO-targeting therapeutics.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Review
Biochemistry & Molecular Biology
Wookyeom Yang, Dasol Kim, Dae Kyoung Kim, Kyung Un Choi, Dong Soo Suh, Jae Ho Kim
Summary: Ovarian cancer is a fatal gynecological malignancy, and its treatment remains a challenge. Cancer stem cells (CSCs) play a key role in cancer relapse and treatment resistance, with their malignancy regulated by cell surface receptors and intracellular factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Jia Mai, Limei Wu, Ling Yang, Ting Sun, Xiaojuan Liu, Rutie Yin, Yongmei Jiang, Jinke Li, Qintong Li
Summary: Epithelial ovarian cancer is a deadly gynecological cancer, and targeting the folate receptor alpha has shown promise in its treatment. Various modalities, including antibody-drug conjugates, monoclonal antibodies, and small molecules, have been explored to exploit this target for effective therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Giulia D. S. Ferretti, Julia Quarti, Gileno dos Santos, Luciana P. Rangel, Jerson L. Silva
Summary: p53 is a mutated tumor suppressor protein that often aggregates and promotes cancer growth. Studying new molecules and therapeutic targets that disrupt p53 aggregates is a promising strategy against cancer. This review classifies anticancer molecules into four categories and highlights the role of autophagy in degrading aggregated p53.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Dermatology
Inger Z. M. Kreuger, Roderick C. Slieker, Tim van Groningen, Remco van Doorn
Summary: Loss of CDKN2A is a common occurrence in melanoma progression and targeting this loss can significantly improve treatment outcomes. Various therapeutic strategies, such as CDK4/6 inhibition, cell cycle dysregulation, metabolic rewiring, epigenetic restoration, co-deleted gene targeting, and modulation of immune responses, have been explored in the context of CDKN2A loss.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Review
Oncology
Adrian Gottschlich, Stefan Endres, Sebastian Kobold
Summary: Interleukin-1 cytokines play a crucial role in inflammation and have implications in cancer research. Clinical trials have shown the potential of IL-1 blockade in cancer treatment, but it may also lead to immune toxicities. Current research focuses on utilizing IL-1 blocking agents to enhance the efficacy and safety of adoptive T cell therapy.
Review
Immunology
Yan Zhao, Yuansong Bai, Meili Shen, Yapeng Li
Summary: Gastric cancer is a highly prevalent and lethal malignancy, and immunotherapy has shown survival benefits for GC patients. Targeted immune cells have emerged as a promising therapeutic strategy in the field of oncology. This review discusses the role and significance of immune cells in the tumor microenvironment of GC and summarizes the current landscape of immunotherapy, including immune checkpoint inhibitors and adoptive cell therapy. While more clinical data is needed, targeting immune cells provides a new direction for GC immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alba Corman, Oleksandra Sirozh, Vanesa Lafarga, Oscar Fernandez-Capetillo
Summary: The nucleolus is where ribosome biogenesis takes place, which is one of the most resource-intensive processes in eukaryotic cells. It is highly responsive to growth signaling and nucleolar insults, collectively known as nucleolar stress. Nucleolar alterations are a prominent feature in various human diseases, including cancer and neurodegeneration, and are also associated with aging. There have been numerous efforts to develop compounds targeting different aspects of nucleolar activity. This article provides an overview of therapeutic opportunities and current therapies for targeting nucleoli in different pathologies.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Mark B. B. Badrov, Daniel A. A. Keir, George Tomlinson, Catherine F. F. Notarius, Philip J. J. Millar, Derek S. S. Kimmerly, J. Kevin Shoemaker, Evan Keys, John S. S. Floras
Summary: This study compared patients with heart failure and healthy controls to identify factors that contribute to augmented muscle sympathetic nerve activity. The results showed that in heart failure patients, muscle sympathetic nerve activity was proportional to heart rate and body mass index, but not related to age, blood pressure, or drug therapy. This study has important implications for personalized therapy.
EUROPEAN JOURNAL OF HEART FAILURE
(2023)
Article
Chemistry, Medicinal
Yihui Song, Shu Wang, Min Zhao, Xinyu Yang, Bin Yu
Summary: SHP2, encoded by PTPN11, is a promising therapeutic target for cancer therapy. However, its multifaceted roles complicate drug discovery. Strategies targeting SHP2, including inhibitors, activators, and PROTAC degraders, have been developed. Protein-protein interactions between SHP2 and other adaptor proteins are also discussed. Target- and pathway-dependent combination strategies of SHP2 for cancer therapy are highlighted.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Yukari Nagao, Akira Yokoi, Kosuke Yoshida, Mai Sugiyama, Eri Watanabe, Kae Nakamura, Masami Kitagawa, Eri Asano-Inami, Yoshihiro Koya, Masato Yoshihara, Satoshi Tamauchi, Yusuke Shimizu, Yoshiki Ikeda, Nobuhisa Yoshikawa, Tomoyasu Kato, Yusuke Yamamoto, Hiroaki Kajiyama
Summary: This study aimed to identify novel targets for uterine leiomyosarcoma (ULMS) through a three-step screening process using a chemical library. The candidates proscillaridin A and lanatoside C showed superior antitumor effects in mouse models. The downregulation of uncoupling protein 2 (UCP2) induced reactive oxygen species (ROS) and suppressed ULMS cell growth, making it a potential therapeutic target.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Yelin Jeong, Ah-Reum Oh, Young Hoon Jung, Hyunjoon Gi, Young Un Kim, Kyeongjin Kim
Summary: Protein ubiquitination plays a crucial role in the activation, translocation, dysregulation, and degradation of proteins. E3 ubiquitin ligases, especially, are important enzymes in this process and have been found to be associated with various metabolic diseases. Understanding the regulatory mechanisms and potential therapeutic targets of E3 ligases and their adaptors can lead to the development of effective treatments for metabolic diseases.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Yelin Jeong, Ah-Reum Oh, Young Hoon Jung, Hyunjoon Gi, Young Un Kim, Kyeongjin Kim
Summary: Posttranslational modification of proteins via ubiquitination plays a crucial role in the development and regulation of metabolic diseases. E3 ubiquitin ligases and their adaptors are important players in this process. Understanding their regulatory mechanisms can lead to the discovery of new therapeutic targets for metabolic diseases.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Milena Samora, Lauro C. Vianna, Jake C. Carmo, Victor Macedo, Matthew Dawes, Aaron A. Phillips, Julian F. R. Paton, James P. Fisher
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2020)
Article
Physiology
Sultan E. AlSalahi, Igor D. Braz, Amar Ahmed, Rehan T. Junejo, James P. Fisher
EXPERIMENTAL PHYSIOLOGY
(2020)
Article
Medicine, General & Internal
Ahsan A. Khan, Rehan T. Junejo, Graham N. Thomas, James P. Fisher, Gregory Y. H. Lip
Summary: AF, regardless of hypertension, is associated with higher HRV, and may be related to vagal tone. Permanent AF has a stronger influence on HRV than paroxysmal AF, indicating autonomic involvement in permanent AF pathophysiology. Exploration of autonomic modulation on cardiovascular system is recommended for future studies.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Physiology
Shigehiko Ogoh, Takuro Washio, Julian F. R. Paton, James P. Fisher, Lonnie G. Petersen
JOURNAL OF APPLIED PHYSIOLOGY
(2020)
Editorial Material
Neurosciences
James P. Fisher
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Physiology
Sultan E. AlSalahi, Rehan T. Junejo, Chris Bradley, George M. Balanos, Christoph Siebenmann, James P. Fisher
Summary: This study investigated the impact of ventilatory response on cerebral perfusion during moderate isocapnic acute hypoxia in humans. The findings suggest that the ventilatory response does not increase cerebral perfusion beyond the changes induced by reduced oxygen saturation, indicating that the body's natural responses to hypoxia adequately regulate cerebral blood flow.
EXPERIMENTAL PHYSIOLOGY
(2021)
Article
Physiology
Eliza Prodel, Thiago Cavalcanti, Helena N. M. Rocha, Maite L. Gondim, Pedro A. C. Mira, James P. Fisher, Antonio C. L. Nobrega
Summary: The study found that beta-adrenergic receptors play a primary role in increasing coronary circulation during handgrip exercise in humans, while coronary blood velocity remains unchanged during metaboreflex activation. The involvement of alpha-adrenergic receptors seems to have limited impact on the control of coronary circulation during handgrip exercise and isolated muscle metaboreflex activation.
EXPERIMENTAL PHYSIOLOGY
(2021)
Article
Neurosciences
Jui-Lin Fan, James P. Fisher
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Physiology
Jui-Lin Fan, Ana Luiza C. Sayegh, Manpreet Kaur, Mathew Dawes, Julian F. R. Paton, James P. Fisher
Summary: In this study, the effects of hypoxia and hyperoxia on venous capacity and compliance in the lower limb were investigated. The results revealed that hypoxia decreased the venous capacity while hyperoxia increased venous compliance.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2022)
Article
Physiology
Charlotte Chen, John Kolbe, Margaret L. Wilsher, Sally De Boer, Julian F. R. Paton, James P. Fisher
Summary: The aim of this study was to investigate the impact of metaboreflex on breathing and dyspnoea in fibrosing interstitial lung disease (FILD). The results showed that activation of metaboreflex did not result in increased respiratory response and dyspnoea ratings in FILD patients. However, the hemodynamic responses after handgrip exercise were attenuated in FILD compared to controls.
EXPERIMENTAL PHYSIOLOGY
(2022)
Article
Neurosciences
Ana Luiza C. Sayegh, Jui-Lin Fan, Lauro C. Vianna, Mathew Dawes, Julian F. R. Paton, James P. Fisher
Summary: This study compared the cardiorespiratory and sympathetic neurocirculatory responses to chemoreflex activation between healthy men and women. The results showed that young women displayed augmented sympathetic responses and attenuated respiratory responses during central chemoreflex activation.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Cardiac & Cardiovascular Systems
James P. Fisher, Johanna Roche, Rachel Turner, Anna Walzl, Giulia Roveri, Hannes Gatterer, Christoph Siebenmann
Summary: This study aimed to investigate the effects of prolonged moderate hypobaric hypoxia on cardiac baroreflex sensitivity in young women and explore the underlying mechanisms. The findings demonstrated that hypoxia decreased the sensitivity, but restoration of inspiratory oxygen partial pressure mitigated this reduction, while voluntary attenuation of pulmonary ventilation had no effect. These results shed light on the role of arterial chemoreflex mechanisms in regulating baroreflex sensitivity during hypobaric hypoxia in young women.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Physiology
Jui-Lin Fan, Ana Luiza C. Sayegh, Thalia Babbage, Mathew Dawes, Julian F. R. Paton, James P. Fisher
Summary: This study investigates the changes in lower limb venous capacity and compliance in hypertensive and normotensive individuals in response to hypoxia and hyperoxia. The results indicate that in hypertensives, hypoxia leads to a decrease in venous capacity and an increase in compliance, while no changes are observed in normotensives.
JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Article
Neurosciences
Ana Luiza C. Sayegh, Jui-Lin Fan, Mathew Dawes, Julian F. R. Paton, James P. Fisher
Summary: The study found that central respiratory and sympathetic chemoreflex sensitivities are increased in hypertensive patients, suggesting that these reflexes may play a role in the development of hypertension.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Surgery
A. Narayanan, M. Naidoo, V. Y. Kong, L. Pearson, K. Mani, J. P. Fisher, M. Khashram, D. L. Clarke
Summary: This study investigates the use of intraoperative music by 110 surgeons in South Africa and their perceptions and attitudes towards its effect on the operating theatre environment. The results show that 80% of respondents reported that music was played at least sometimes, and 74% enjoyed it. Overall, background music in the operating theatre was seen to have a positive impact on surgeons' temperament, focus, mood, and performance, though communication concerns were raised by some participants. Further interventional and qualitative studies are needed to explore these findings.
SOUTH AFRICAN JOURNAL OF SURGERY
(2023)