A5063687936- Hormonal Regulation and Hypertension
- Adrenal Hormones and Disorders
- Spine and Intervertebral Disc Pathology
- Musculoskeletal pain and rehabilitation
- Myofascial pain diagnosis and treatment
- Nosocomial Infections in ICU
- COVID-19 Clinical Research Studies
- Inflammasome and immune disorders
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Medical Imaging and Analysis
- Circadian rhythm and melatonin
- Advanced Neuroimaging Techniques and Applications
- Kawasaki Disease and Coronary Complications
- Epigenetics and DNA Methylation
- Pharmacological Effects of Natural Compounds
- Nutrition and Health in Aging
- COVID-19 diagnosis using AI
- Pluripotent Stem Cells Research
- COVID-19 Impact on Reproduction
- Estrogen and related hormone effects
- Apelin-related biomedical research
- Spaceflight effects on biology
- Knee injuries and reconstruction techniques
- Cardiovascular Disease and Adiposity
University of Cambridge
2020-2024
First Affiliated Hospital of Kunming Medical University
2017-2024
Kunming Medical University
2017-2024
Cancer Research UK Cambridge Center
2023-2024
Addenbrooke's Hospital
2023
Manchester Academic Health Science Centre
2018-2020
University of Manchester
2018-2020
Hutchison/MRC Research Centre
2020
University of Edinburgh
2011-2017
The Queen's Medical Research Institute
2016-2017
Abstract Pharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation senolytic therapies to human is hampered by their suboptimal specificity cells and important toxicities that narrow therapeutic windows. We have previously shown the high levels senescence‐associated lysosomal...
The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, liver was significantly more sensitive during day. Temporal segregation action underpinned physical interaction GR with...
Pulmonary airway epithelial cells (AECs) form a critical interface between host and environment. We investigated the role of circadian clock using mice bearing targeted deletion gene brain muscle ARNT-like 1 (
ABSTRACT The circadian clock is a critical regulator of immune function. We recently highlighted role for the in mouse model pulmonary inflammation. epithelial protein Bmal1 was required to regulate neutrophil recruitment response inflammatory challenge. regulated glucocorticoid receptor (GR) chemokine, CXC chemokine ligand 5 (CXCL5), providing candidate mechanism. now show that control neutrophilia persists without rhythmic availability. Epithelial GR‐null mice had elevated expression...
There is an interaction between the lumbar spine and paraspinal muscles, which may play a role in development of intervertebral disc (IVD) degeneration affect CLBP. The study aims to assess relationship IVD muscle fat infiltration CLBP patients by quantitative MR imaging, evaluate influence sex age on infiltration. Sixty (46.3 years ±17.0) thirty-two healthy subjects (44.9 ±17.6) were recruited for this study. 3.0 T MRI was used perform sagittal axial T1, T2 spine, IDEAL imaging at L4/5...
Accompanied with intervertebral disc (IVD) degeneration, increasing fat infiltration of paraspinal muscles may be related to discogenic low back pain (DLBP), but their relationship is still unclear and the classical animal models are not completely applicable. The purpose this study was assess muscle in patients DLBP by quantitative MRI, develop a novel rat model explore potential between TNF-α levels. We measured proton density fraction (PDFF) multifidus erector spinae 70 36 healthy...
11β-Hydroxysteroid dehydrogenase type-1 (11β-HSD1) converts inert cortisone into active cortisol, amplifying intracellular glucocorticoid action. 11β-HSD1 deficiency improves cardiovascular risk factors in obesity but exacerbates acute inflammation. To determine the effects of on atherosclerosis and its inflammation, atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice were treated with a selective inhibitor or crossed 11β-HSD1-KO to generate double knockouts (DKOs) challenged an...
Objective Selective decontamination of the digestive tract (SDD) is a well-studied but hotly contested medical intervention enhanced infection control. Here, we aim to characterise changes microbiome and antimicrobial resistance (AMR) gene profiles in critically ill children treated with SDD-enhanced control compared conventional Design We conducted shotgun metagenomic resistome analysis on serial oropharyngeal faecal samples collected from ill, mechanically ventilated patients pilot...
Endogenous glucocorticoid action within cells is enhanced by prereceptor metabolism 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts intrinsically inert cortisone and 11-dehydrocorticosterone into active cortisol corticosterone, respectively. 11β-HSD1 highly expressed in immune elicited to the mouse peritoneum during thioglycollate-induced peritonitis down-regulated as inflammation resolves. During inflammation, 11β-HSD1-deficient mice show recruitment of inflammatory...
Abstract Purpose Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test LRTI inform better use antimicrobials. Methods The Rapid Assay Sick Children Acute Lung Study was single-centre, prospective, observational cohort study mechanically...
Chronically elevated glucocorticoid levels impair cognition and are pro-inflammatory in the brain. Deficiency or inhibition of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), which converts inactive into active glucocorticoids, protects against glucocorticoid-associated chronic stress- age-related cognitive impairment. Here, we hypothesised that 11β-HSD1 deficiency attenuates brain cytokine response to inflammation. Because inflammation is associated with altered energy metabolism, also...
Abstract Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single omics to compare process acute respiratory COVID-19 and those presenting non infections children. show that Multi-Inflammatory Syndrome Children (MIS-C), natural killer monocyte population demonstrate heightened CD95 (Fas) Interleuking 18 expression. Additionally, TCR CD4+ T-cells exhibit skewed...
11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) predominantly converts inert glucocorticoids into active forms, thereby contributing to intracellular glucocorticoid levels. 11β-HSD1 is dynamically regulated during inflammation, including in macrophages where it regulates phagocytic capacity. The resolution of inflammation some disease models inflammatory arthritis impaired by deficiency or inhibition. However, deficiency/inhibition also promotes angiogenesis, which beneficial mouse surgical...
It is crucial to explore the pathogenesis of major depressive disorder (MDD) at early stage for better diagnostic and treatment strategies. was suggested that MDD might be involving in functional or structural alternations brain network level. However, onset MDD, whether whole white matter (WM) alterations level are already evident still remains unclear. In present study, diffusion MRI scanning adopt depict unique WM topology across entire MDD. Twenty-one first episode, short duration (<1...
Abstract This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with strength in patients type 2 diabetes mellitus (T2DM). Seventy T2DM and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T isokinetic measurements obtain skeletal index (SMI), intermuscular adipose tissue (IMAT) proton density fraction (PDFF), intramuscular (IMF) PDFF, peak torque (PT) total work (TW) knee extensors flexors. The differences between asymptomatic...
To investigate the dynamic changes in high-resolution computed tomography (HRCT) findings of coronavirus disease 2019 (COVID-19) patients with different severities stages.We retrospectively collected clinical and imaging data 96 Yunnan Province, China, who were diagnosed COVID-19 between January 22 March 15, 2020. Based on severity, classified into four types: mild (n=15), moderate (n=59), severe (n=19), critical (n=3). hospital stay number (CT) scans, clinical/disease course was divided...
Approximately 40% of patients with acute low back pain (LBP) develop chronic pain, which significantly increases the risk poor prognosis. To reduce LBP becoming chronic, effective preventive strategies are needed. Early identification factors for development can help clinicians choose appropriate treatment options and improve patient outcomes. However, previous screening tools have not considered medical imaging findings. The aim this study is to identify that predict based on clinical...
Introduction Lower respiratory tract infection (LRTI) is the most commonly treated in critically ill children. Pathogens are infrequently identified on routine culture, and this a time-consuming process. A syndromic approach to rapid molecular testing that includes wide range of bacterial fungal targets has potential aid clinical decision making reduce unnecessary broad spectrum antimicrobial prescribing. Here, we describe single-centre prospective cohort study investigating use 52-pathogen...
Abstract Background The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of spine. Therefore, aim this study was to investigate relationship between fat infiltration vertebral body related changes [vertebral bone quality (VBQ) score Modic (MCs)] patients with chronic low back pain (CLBP). Methods Patients CLBP were prospectively collected four hospitals all underwent 3.0T magnetic resonance scanning. Basic clinical information collected, including...
Oncogenic transformation and Oct4, Sox2, Klf4 c-Myc (OSKM)-mediated induction of pluripotency are two independent incompatible cellular fates. While continuous expression OSKM can convert normal somatic cells into teratogenic pluripotent cells, it remains speculative what is the impact transient in cancer cells. Here, we find that limits growth transformed lung by inducing apoptosis senescence. We identify Oct4 as main individual reprogramming factors responsible for this effect....