Review
Immunology
Kiran Thakur, Heena Khan, Amarjot Kaur Grewal, Thakur Gurjeet Singh
Summary: Orphan receptors, a subsection of nuclear receptors, have been linked to neuroinflammation and neurodegenerative diseases. PPAR gamma, NR4As, and orphan GPCRs hold high potential as therapeutic targets for preventing these disorders.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Chokdee Wongborisuth, Sukanya Chumchuen, Orapan Sripichai, Usanarat Anurathaphan, Nuankanya Sathirapongsasuti, Duantida Songdej, Amornrat Tangprasittipap, Suradej Hongeng
Summary: This study found that ZNF802 may act as a transcriptional repressor of the gamma-globin gene in adult erythroid cells. Deficiency in ZNF802 induced induction of HBG expression and increased HbF levels in beta(0)-thalassemia/hemoglobinE erythroblasts.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Nikita Sandhu, Satyavati Rana, Kiran Meena
Summary: NR5A2 is a nuclear receptor involved in various biological processes, with implications in diseases such as chronic pancreatitis and pancreatic cancer. Its activity is regulated by intracellular phospholipids, although its specific ligand remains unknown. Future emphasis is needed on discovering small molecule agonists and antagonists for therapeutic applications.
MOLECULAR BIOLOGY REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Charlotte Scholtes, Vincent Giguere
Summary: The article discusses the generation and role of reactive oxygen species, highlighting the estrogen-related receptors as master regulators of ROS metabolism, which can contribute to uncovering new therapeutic strategies.
Review
Endocrinology & Metabolism
Minas Sakellakis
Summary: This review discusses the role of orphan receptors in prostate cancer, focusing on their unknown endogenous ligands and their significant impact on tumor growth and progression.
Review
Biochemistry & Molecular Biology
Yuliang Wang, Weijie Gao, Youjia Li, Sin Ting Chow, Wenjuan Xie, Xingxing Zhang, Jianfu Zhou, Franky Leung Chan
Summary: Prostate cancer relies on the androgen receptor-mediated signaling for growth, making hormone or androgen-deprivation therapy a key treatment option. Despite its effectiveness in locally advanced or metastatic cases, most patients will develop resistance, leading to castration-resistant disease or even a more aggressive androgen-independent subtype. These newly identified orphan nuclear receptors (ONRs) have shown potential as biomarkers and therapeutic targets in advanced prostate cancer.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Cullen M. Lilley, Andrea Alarcon, My-Huyen Ngo, Jackeline S. Araujo, Luis Marrero, Kimberlee S. Mix
Summary: The orphan nuclear receptor 4A2 (NR4A2/Nurr1) plays an important role in the development of rheumatoid arthritis (RA) and is overexpressed in inflamed synovium. The expression of NR4A2 and its upstream regulator, nuclear factor kappa B (NF-kappa B), increases during disease progression, early expressed in inflamed synovium. Screening of RA-related genes revealed that NR4A receptors and NF-kappa B-1 play central regulatory roles in this model.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Almira B. Ocampo, Joseph Gregory Z. Cabinta, Hyvi Valerie J. Padilla, Eizadora T. Yu, Ricky B. Nellas
Summary: Using in silico methods, this study investigates the molecular basis of monoterpene interactions with OARs/TARs in insects, and identifies carvacrol as a potential natural-product-based insecticide that targets multiple insect pests while being nonharmful to honeybees and Asian swallowtail butterflies. This research provides insights into the development of effective species-specific and environmentally friendly insecticides.
Article
Immunology
Christina Stehle, Timo Rueckert, Remi Fiancette, Dominika W. Gajdasik, Claire Willis, Carolin Ulbricht, Pawel Durek, Mir-Farzin Mashreghi, Daniela Finke, Anja Erika Hauser, David R. Withers, Hyun-Dong Chang, Jakob Zimmermann, Chiara Romagnani
Summary: The study reveals the unexpected roles of T-bet and ROR alpha during embryonic ILC function, with ROR gamma t being crucial in counteracting the suppressive effects of T-bet. Deficiency of T-bet rescues lymph node formation in ROR gamma t-deficient mice by skewing the differentiation fate of fetal ILCs.
Article
Biochemistry & Molecular Biology
Xinyu Li, Mengxia Chen, Biru Liu, Peifen Lu, Xiang Lv, Xiang Zhao, Shuaiying Cui, Peipei Xu, Yukio Nakamura, Ryo Kurita, Bing Chen, David C. S. Huang, De-Pei Liu, Ming Liu, Quan Zhao
Summary: The study demonstrates that NonO interacts with SOX6 to repress gamma-globin gene expression in human erythroid cells, and depletion of NonO results in significant activation of gamma-globin expression. In vivo experiments using mice also confirm the role of NonO in reactivating globin gene expression, suggesting a conserved function of NonO during mammalian evolution.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Tajana Sajinovic, Gottfried Baier
Summary: Following gene expansion, the NR2F family of nuclear orphan receptors in mammals consists of three isoforms: NR2F1, NR2F2, and NR2F6. NR2F1 and NR2F2 are closely related, while NR2F6 shows more biochemical divergence. This review highlights the cellular functions of NR2F family members, with a focus on their involvement in carcinogenesis. The expression patterns and functions of the isoforms are non-redundant, and NR2F2 appears to be functionally more similar to NR2F6 than NR2F1. Enhanced expression of NR2F isoforms has been identified as prognostic biomarkers in various cancers, suggesting their potential as therapeutic targets. Overall, NR2F family nuclear receptors play a critical role in regulating proliferation and differentiation in health and disease.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Article
Geriatrics & Gerontology
Waly Dioh, Vihang Narkar, Anurag Singh, Fady Malik, Luigi Ferrucci, Cendrine Tourette, Jean Mariani, Rob van Maanen, Roger A. Fielding
Summary: In recent years, new classes of therapies have been investigated, aiming to restore or improve physical functioning in older adults. These include Mas receptor agonists, regulators of mitophagy, skeletal muscle troponin activators, anti-inflammatory compounds, and targets of orphan nuclear receptors. This article summarizes recent developments on the function-promoting effects of these compounds, providing preclinical and clinical data on their safety and efficacy. The development of novel compounds in this area is expanding and may lead to a new treatment paradigm for age-associated mobility loss and disability.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Dermatology
Anna A. Brozyna, Michal A. Zmijewski, Kinga Linowiecka, Tae-Kang Kim, Radomir M. Slominski, Andrzej T. Slominski
Summary: The pathogenesis of inflammatory skin diseases is associated with abnormal activity of keratinocytes and immune cells infiltrate. Vitamin D-3 deficiency can be correlated with increased incidence, severity and duration of inflammatory skin disorders. Our study found disturbed expression of LRP2/megalin, VDR, ROR alpha and ROR gamma in inflammatory skin lesions compared to normal skin. Changes in the activity of these proteins may play a role in the pathogenesis of inflammatory skin disorders and could serve as potential targets for therapy.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Eun-Jin Wang, Young-Cheon Kim, Jeong Hwan Lee, Jeong-Kook Kim
Summary: In this study, the nuclear localization signal (NLS) of Arabidopsis SF1 protein (AtSF1) was characterized, revealing the importance of the RKRKSRWADDE sequence for the complete nuclear localization of the protein. At least two basic amino acid residues within this motif were found to be crucial for the function of AtSF1 protein, indicating a unique feature of NLS in plant SF1 proteins compared to fungal and metazoan counterparts.
PLANT BIOTECHNOLOGY REPORTS
(2021)
Article
Gastroenterology & Hepatology
Palak Ahuja, Xinyi Bi, Chun Fai Ng, Margaret Chui Ling Tse, Miaojia Hang, Brian Pak Shing Pang, Elsie Chit Yu Iu, Wing Suen Chan, Xin Ci Ooi, Anqi Sun, Oana Herlea-Pana, Zhixue Liu, Xiuying Yang, Baowei Jiao, Xin Ma, Kelvin Ka Lok Wu, Leo Tsz On Lee, Kenneth King Yip Cheng, Chi Wai Lee, Chi Bun Chan
Summary: This study found that SBK1 is a regulator of hepatic lipid metabolism and systemic insulin sensitivity in response to obesity through the Nur77-FGF21 pathway.
Article
Anatomy & Morphology
Jennie N. Jeyapalan, Victoria. James, David S. Gardner, Jennifer H. Lothion-Roy, Nigel P. Mongan, Catrin Sian Rutland
Summary: Research is an essential part of veterinary medicine degrees, and remote learning during the COVID-19 pandemic has affected the performance and experience of students. This study analyzed the outcomes and feedback of students who completed independent research projects, showing that the pandemic cohorts achieved higher grades with increased access to resources while facing challenges in workload management and conceptual exploration.
ANATOMIA HISTOLOGIA EMBRYOLOGIA
(2023)
Article
Cell Biology
Nehal M. Atallah, Michael S. Toss, Andrew R. Green, Nigel P. Mongan, Graham Ball, Emad A. Rakha
Summary: This study refined the definition of HER2-low breast cancer based on correlation with HER2 mRNA and successfully distinguished between HER2 IHC score 1+ and score 0 tumors. The refined criteria showed higher observer agreement compared to the original clinical scores.
Review
Pathology
Suzan F. Ghannam, Catrin Sian Rutland, Cinzia Allegrucci, Nigel P. Mongan, Emad Rakha
Summary: Basement membrane (BM) is an important structure separating the epithelium from the stroma, and its composition varies during different stages of breast development. In pathological conditions, the presence or absence of BM plays a crucial role in distinguishing in situ from invasive lesions. Although diagnostic techniques are evolving, BM is still considered a useful marker in ambiguous cases. This review discusses the structure, function, and clinical significance of BM in relation to breast lesions, with a focus on differentiating it from alternative pathological tissue.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Oncology
Jaclyn M. Kubala, Kristian B. Laursen, Ryan Schreiner, Ryan M. Williams, Johannes C. van der Mijn, Michael J. Crowley, Nigel P. Mongan, David M. Nanus, Daniel A. Heller, Lorraine J. Gudas
Summary: In clear cell renal cell carcinoma (ccRCC), overexpression of NDUFA4L2 contributes to ccRCC proliferation and survival. NDUFA4L2 enhances glycolysis and regulates mitochondrial-lysosomal associations in ccRCC. Knocking out NDUFA4L2 decreases lysosomal size and abundance in ccRCC cells.
CANCER BIOLOGY & THERAPY
(2023)
Article
Genetics & Heredity
Jennifer Lothion-Roy, Daisy B. Haigh, Anna E. Harris, Veronika M. Metzler, Mansour Alsaleem, Michael S. Toss, Yousif Kariri, Atara Ntekim, Brian D. Robinson, Francesca Khani, Lorraine J. Gudas, Cinzia Allegrucci, Victoria H. James, Srinivasan Madhusudan, Melissa Mather, Richard D. Emes, Nathan Archer, Rupert G. Fray, Emad Rakha, Jennie N. Jeyapalan, Catrin S. Rutland, Nigel P. Mongan, Corinne L. Woodcock
Summary: N-6-methyladenosine (m(6)A) is the most abundant internal mRNA modification and plays crucial roles in gene expression, RNA stability, splicing and translation. The components of the m(6)A modification have been implicated in diseases, including prostate cancer (PCa). This study investigated the expression and clinical significance of METTL3, METTL14, WTAP, and CBLL1 in PCa specimens and cell lines, and found that METTL3 and CBLL1 expression were associated with poorer PCa patient outcomes. Functional analysis revealed the roles of METTL3 in androgen receptor regulation and gene expression in PCa cells.
FRONTIERS IN GENETICS
(2023)
Review
Pharmacology & Pharmacy
Juliette Brownlie, Sanat Kulkarni, Mashael Algethami, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: DNA repair targeted therapeutics, such as PARP inhibitors, have shown promising results in the treatment of BRCA germline deficient breast and ovarian cancer. However, not all patients respond to this treatment due to intrinsic or acquired resistance. Therefore, the exploration of other synthetic lethality approaches, including ATM, ATR, and WEE1 inhibitors, is currently an active area in cancer research.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Article
Cell Biology
Suzan F. Ghannam, Catrin S. Rutland, Cinzia Allegrucci, Nigel P. Mongan, Emad Rakha
Summary: This study describes the geometric characteristics of the EPC capsule and provides evidence that it is a reactive process rather than a thickened native BM characteristic of normal and in situ lesions. The study supports the understanding that EPC is an indolent invasive carcinoma based on capsule characteristics.
Article
Cell Biology
Ayat G. Lashen, Michael S. Toss, Louisa Wootton, Andrew R. R. Green, Nigel P. Mongan, Srinivasan Madhusudan, Emad Rakha
Summary: This study aimed to evaluate the prognostic and predictive role of PLK1 in breast cancer (BC) and its molecular subtypes. The results showed that high PLK1 expression was significantly associated with better outcome in the whole cohort and luminal BC, but with poorer outcome in triple-negative breast cancer (TNBC).
Review
Pathology
Ayat Gamal Lashen, Michael S. Toss, Suzan Fathy Ghannam, Shorouk Makhlouf, Andrew Green, Nigel P. Mongan, Emad Rakha
Summary: Ki67 expression is an important and cost-effective surrogate marker for assessing tumour cell proliferation in breast cancer. It has prognostic and predictive value, especially in hormone receptor-positive, HER2-negative tumours. However, challenges exist in its routine clinical use and there is increasing criticism of its clinical utility. Overcoming these challenges and weighing the benefits against weaknesses are necessary to maximize its performance in breast cancer.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Immunology
Shahd Talhouni, Wakkas Fadhil, Nigel P. Mongan, Lara Field, Kelly Hunter, Sogand Makhsous, Alexandre Maciel-Guerra, Nayandeep Kaur, Ausrine Nestarenkaite, Arvydas Laurinavicius, Benjamin E. Willcox, Tania Dottorini, Ian Spendlove, Andrew M. Jackson, Mohammad Ilyas, Judith M. Ramage
Summary: The characterization of the tumour immune infiltrate, specifically CD8+ T-cells, has a strong predictive survival value for cancer patients. A study found that the abundance and localization of activated tumour-specific tissue resident memory CD8 T-cells (T-RM) can provide a higher-resolution route to patient stratification.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Veronika M. Metzler, Simone de Brot, Daisy B. Haigh, Corinne L. Woodcock, Jennifer Lothion-Roy, Anna E. Harris, Emeli M. Nilsson, Atara Ntekim, Jenny L. Persson, Brian D. Robinson, Francesca Khani, Kristian B. Laursen, Lorraine J. Gudas, Michael S. Toss, Srinivasan Madhusudan, Emad Rakha, David M. Heery, Catrin S. Rutland, Nigel P. Mongan, Jennie N. Jeyapalan
Summary: KDM1A and KDM5B play crucial roles in prostate cancer by promoting androgen regulated gene expression through interaction with AR. Developing therapies targeting KDM1A and KDM5B is of great importance due to the ineffectiveness of conventional androgen deprivation therapies and androgen receptor signalling inhibitors in castrate resistant prostate cancer (CRPC).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Mashael Algethami, Michael S. S. Toss, Corinne L. L. Woodcock, Chandar Jaipal, Juliette Brownlie, Ahmed Shoqafi, Adel Alblihy, Katia A. A. Mesquita, Andrew R. R. Green, Nigel P. P. Mongan, Jennie N. N. Jeyapalan, Emad A. A. Rakha, Srinivasan Madhusudan
Summary: This study found that Replication Protein A (RPA) plays a critical role in breast cancer, being involved in cell DNA replication, checkpoint regulation and DNA repair. Low levels of RPA are associated with aggressive breast cancer and shorter survival outcomes. The study suggests that a precision oncology strategy targeting RPA is feasible in breast cancer patients.
Article
Oncology
Shorouk Makhlouf, Noorul Wahab, Michael Toss, Asmaa Ibrahim, Ayat G. Lashen, Nehal M. Atallah, Suzan Ghannam, Mostafa Jahanifar, Wenqi Lu, Simon Graham, Nigel P. Mongan, Mohsin Bilal, Abhir Bhalerao, David Snead, Fayyaz Minhas, Shan E. Ahmed Raza, Nasir Rajpoot, Emad Rakha
Summary: In this study, artificial intelligence (AI) was used to assess the prognostic significance of tumour infiltrating lymphocytes (TILs) in a large cohort of luminal breast cancer patients. The results showed that TILs counts and their spatial distribution had predictive value for the prognosis of early-stage breast cancer patients.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
N. M. Atallah, M. Alsaleem, M. S. Toss, N. P. Mongan, E. Rakha
Summary: HER2-positive breast cancer subtypes exhibit differential responses to targeted anti-HER2 therapy. Patients with IHC 2+/Amplified subtype have lower pathological complete response rates and shorter survival. ER positivity significantly decreases response to anti-HER2 therapy in IHC 2+/Amplified patients.
BRITISH JOURNAL OF CANCER
(2023)
Review
Oncology
Mosebo Armstrong Manabile, Rodney Hull, Richard Khanyile, Thulo Molefi, Botle Precious Damane, Nigel Patrick Mongan, David Owen Bates, Zodwa Dlamini
Summary: Colorectal cancer is a leading cause of cancer-related deaths globally, with increasing incidence in developing countries. Dysregulated alternative splicing processes in colorectal cancer can promote its development and progression by producing proteins that activate cancer-promoting genes or deactivate cancer-inhibiting genes. It is important to identify these dysregulated alternative splicing genes in order to develop targeted treatments and diagnostics to stop cancer development and progression.