A5074658559- Osteoarthritis Treatment and Mechanisms
- Cancer-related molecular mechanisms research
- Total Knee Arthroplasty Outcomes
- Adipose Tissue and Metabolism
- Inflammatory mediators and NSAID effects
- Muscle Physiology and Disorders
- RNA Interference and Gene Delivery
- Bone Metabolism and Diseases
- Orthopaedic implants and arthroplasty
- Adipokines, Inflammation, and Metabolic Diseases
- Muscle metabolism and nutrition
- Lower Extremity Biomechanics and Pathologies
- Nutrition and Health in Aging
- Circular RNAs in diseases
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- Ion channel regulation and function
- Cytokine Signaling Pathways and Interactions
- RNA modifications and cancer
- Bone health and treatments
- Pharmacological Effects and Assays
- Exercise and Physiological Responses
- RNA Research and Splicing
- Rheumatoid Arthritis Research and Therapies
- Bone health and osteoporosis research
University of Birmingham
2016-2025
Versus Arthritis
2018-2025
NIHR Birmingham Biomedical Research Centre
2018-2025
Queen Elizabeth Hospital
2018-2025
Queen Elizabeth Hospital Birmingham
2015-2024
Musgrove Park Hospital
2023
AstraZeneca (United Kingdom)
2004-2019
The Ohio State University Wexner Medical Center
2019
University College London
2019
Campbellsville University
2019
Skeletal muscle atrophy occurs as a consequence of injury, illness, surgery, and disuse, impacting appreciably on health care costs patient quality life, particularly in the absence appropriate rehabilitation. The molecular mechanisms that regulate mass during rehabilitation humans have not been elucidated, despite several robust candidate pathways being identified. Here, we induced skeletal healthy volunteers using two weeks limb immobilization, then stimulated restoration with six...
Cell-penetrating peptides such as antennapedia, TAT, transportan and polyarginine have been extensively employed for in vitro vivo delivery of biologically active peptides. However, little is known the relative efficacy, toxicity uptake mechanism individual protein transduction domain-peptide conjugates, factors that will be critical determining most effective sequence. In present study, we show by FACS analysis unconjugated demonstrate similar kinetic profiles, being maximal at 1-3 h...
The therapeutic application of siRNA shows promise as an alternative approach to small-molecule inhibitors for the treatment human disease. However, major obstacle its use has been difficulty in delivering these large anionic molecules vivo. In this study, we have investigated whether siRNA-mediated knockdown p38 MAP kinase mRNA mouse lung is influenced by conjugation nonviral delivery vector cholesterol and cell penetrating peptides (CPP) TAT(48−60) penetratin. Initial studies fibroblast...
The association of obesity with both hand and knee osteoarthritis (OA) is suggestive a link between dysfunctional metabolism joint integrity. Given the role adipokines in mediating bone cartilage homeostasis, we undertook this study to examine relationship biomarkers population subjects OA, determine whether adipokine levels predicted 2-year integrity.One hundred seventeen underwent magnetic resonance imaging at baseline followup. Cartilage volume was assessed from these images. Serum were...
Increasing evidence suggests that inflammation plays a central role in driving joint pathology certain patients with osteoarthritis (OA). Since many OA are obese and increased adiposity is associated chronic inflammation, we investigated whether hip exhibited differential pro-inflammatory cytokine signalling peripheral local lymphocyte populations, compared to normal weight patients. No differences either blood or populations were found between normal-weight However, synovial fibroblasts...
Objective To identify long noncoding RNAs (lncRNAs), including intergenic (lincRNAs), antisense RNAs, and pseudogenes, associated with the inflammatory response in human primary osteoarthritis (OA) chondrocytes to explore their expression function OA. Methods OA cartilage was obtained from patients hip or knee following joint replacement surgery. Non‐OA postmortem donors fracture of neck femur. Primary were isolated by collagenase digestion. LncRNA analysis performed RNA sequencing (RNAseq)...
A method for the production of complex cell-laden structures is reported, which allows high-levels spatial control over mechanical and chemical properties. The potential this producing complicated tissues demonstrated by manufacturing a hard/soft tissue interface demonstrating that cell phenotype can be maintained four weeks culture.
The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary cells (ASMCs), whereas changed expression has been observed CD8 T from patients asthma.
Synovial inflammation is associated with pain severity in patients knee osteoarthritis (OA). The aim here was to determine a population OA, whether synovial tissue from areas exhibited different fibroblast subsets, compared sites not pain. A further compare differences between early and end-stage disease subsets.Patients OA (n = 29) 22) were recruited. Patient reported recorded by questionnaire using an anatomical map. Proton density fat suppressed MRI axial sagittal sequences analysed...
Abstract By interacting with proteins and nucleic acids, the vast family of mammalian circRNAs is proposed to influence many biological processes. Here, RNA sequencing analysis differentially expressed during myogenesis revealed that circSamd4 expression increased robustly in mouse C2C12 myoblasts differentiating into myotubes. Moreover, silencing circSamd4, which conserved between human mouse, delayed lowered myogenic markers cultured from both species. Affinity pulldown followed by mass...
Abstract Background Osteoarthritis (OA), a multifaceted condition, poses significant challenge for the successful clinical development of therapeutics due to heterogeneity. However, classifying molecular endotypes OA pathogenesis could provide invaluable phenotype‐directed routes stratifying subgroups patients targeted therapeutics, leading greater chances success in trials. This study establishes soft joint tissue driven by obesity both load‐bearing and non‐load bearing joints. Methods...
The existing suite of therapies for bone diseases largely act to prevent further loss but fail stimulate healthy formation and repair. We describe an endogenous osteopeptide (PEPITEM) with anabolic osteogenic activity, regulating remodeling in health disease. PEPITEM acts directly on osteoblasts through NCAM-1 signaling promote their maturation new bone, leading enhanced trabecular growth strength. Simultaneously, stimulates inhibitory paracrine loop: promoting osteoblast release the decoy...
Synthetic siRNA duplexes are used widely as reagents for silencing of mRNA targets in cells and being developed vivo use. Serum stability is a major concern if to be therapeutic delivery within blood circulation. We have the use MALDI-TOF mass spectrometry rapid convenient analytical tool identify most vulnerable sites serum degradation. Using this approach, we found that one duplex (Dh3) with UpA sequences close end was particularly cleavage. This produced fragment consistent presence...
Substance P (SP, 2.5–10 μ m ) was applied by rapid bath perfusion to bullfrog lumbar sympathetic neurones in vitro , voltage‐clamped through a single micro‐electrode. In unclamped cells, SP produced depolarization accompanied an increase apparent input resistance. Under voltage‐clamp voltage‐dependent inward current induced SP, during which the time‐dependent relaxations square voltage commands were inhibited. It is concluded that inhibits M‐current (I M ), species of K + ‐current, and I...
Studies in murine cell lines and mouse models suggest that IL-15 promotes myogenesis may protect against the inflammation-mediated skeletal muscle atrophy which occurs sarcopenia cachexia. The effects of on human growth development remain largely uncharacterised. Myogenic cultures were isolated from young elderly subjects. Myoblasts differentiated for 8 d, with or without addition recombinant cytokines (rIL-15, rTNFα) an receptor neutralising antibody. Although myotubes 19% thinner derived...
To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients osteoarthritis (OA), and to explore expression function these lncRNAs.Synovium was collected normal-weight hip fracture (non-OA; n = 6) (n 8) OA. Expression RNA determined by RNA-sequencing quantitative reverse transcription-polymerase chain reaction. Knockdown lncRNA performed using LNA-based GapmeRs. Synovial fibroblast cytokine production measured enzyme-linked...