Publications by authors named "M Patrice Lindsay"

617 Publications

Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets.

EBioMedicine 2021 Oct 7;72:103618. Epub 2021 Oct 7.

Institute of Inflammation and Ageing, MRC-ARUK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, United Kingdom. Electronic address:

Background: Synovial inflammation is associated with pain severity in patients with knee osteoarthritis (OA). The aim here was to determine in a population with knee OA, whether synovial tissue from areas associated with pain exhibited different synovial fibroblast subsets, compared to synovial tissue from sites not associated with pain. A further aim was to compare differences between early and end-stage disease synovial fibroblast subsets.

Methods: Patients with early knee OA (n = 29) and end-stage knee OA (n = 22) were recruited. Patient reported pain was recorded by questionnaire and using an anatomical knee pain map. Proton density fat suppressed MRI axial and sagittal sequences were analysed and scored for synovitis. Synovial tissue was obtained from the medial and lateral parapatellar and suprapatellar sites. Fibroblast single cell RNA sequencing was performed using Chromium 10X and analysed using Seurat. Transcriptomes were functionally characterised using Ingenuity Pathway Analysis and the effect of fibroblast secretome on neuronal growth assessed using rat DRGN.

Findings: Parapatellar synovitis was significantly associated with the pattern of patient-reported pain in knee OA patients. Synovial tissue from sites of patient-reported pain exhibited a differential transcriptomic phenotype, with distinct synovial fibroblast subsets in early OA and end-stage OA. Functional pathway analysis revealed that synovial tissue and fibroblast subsets from painful sites promoted fibrosis, inflammation and the growth and activity of neurons. The secretome of fibroblasts from early OA painful sites induced greater survival and neurite outgrowth in dissociated adult rodent dorsal root ganglion neurons.

Interpretation: Sites of patient-reported pain in knee OA exhibit a different synovial tissue phenotype and distinct synovial fibroblast subsets. Further interrogation of these fibroblast pathotypes will increase our understanding of the role of synovitis in OA joint pain and provide a rationale for the therapeutic targeting of fibroblast subsets to alleviate pain in patients.

Funding: This study was funded by Versus Arthritis, UK (21530; 21812).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2021.103618DOI Listing
October 2021

Pre-concentration of microRNAs by LNA-modified magnetic beads for enhancement of electrochemical detection.

Sci Rep 2021 Oct 4;11(1):19650. Epub 2021 Oct 4.

Department of Electronic and Electrical Engineering, University of Bath, Bath, BA2 7AY, UK.

MicroRNAs are extremely promising candidates for early cancer diagnosis and prognosis. The levels of circulating microRNAs provide valuable information about cancer disease at its early stages. However, the levels of microRNAs that need to be detected are extremely low and difficult to discriminate from a large pool of oligonucleotides. There is the need for accurate, rapid and sensitive detection methodologies for detection of microRNAs. We developed electrochemical impedance spectroscopy peptide nucleic acid (PNA)-based sensors that can detect miRNAs in diluted serum with a limit of detection of 0.38 fM. In order to further improve the accuracy and reliability of the sensors, we developed an assay using magnetic beads for simple and rapid fishing of target microRNAs from solution and its pre-concentration prior to electrochemical detection. Our methodology utilizes magnetic beads for the capture of the target microRNA from solution and brings the concentrated sample to the sensor surface. We modify the magnetic beads with locked nucleic acids (LNA), which have high affinity and specificity to their complementary microRNA sequence. The separated and concentrated microRNA is then detected using the PNA-based sensors. By exposing the sensing electrodes only to the captured microRNAs, interferences from other nucleotides or biomolecules from the sample are eliminated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-99145-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490432PMC
October 2021

Case 30-2021: A 47-Year-Old Man with Recurrent Unilateral Head and Neck Pain.

N Engl J Med 2021 Sep;385(14):1317-1325

From the Departments of Medicine (M.E.L., D.M.D.), Pediatrics (M.E.L., J.V.T.), Radiology (B.C.Y.), and Surgery (M.R.J.), Massachusetts General Hospital, and the Departments of Medicine (M.E.L., D.M.D., M.R.J.), Pediatrics (M.E.L., J.V.T.), and Radiology (B.C.Y.), Harvard Medical School - both in Boston.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMcpc2107347DOI Listing
September 2021

Sound Stimulation Can Affect Growth and Production of Volatile Metabolites in Liquid Medium.

Metabolites 2021 Sep 7;11(9). Epub 2021 Sep 7.

School of Biological Sciences, University of Auckland, 3A Symonds Street, Auckland 1010, New Zealand.

The biological effect of sound on microorganisms has been a field of interest for many years, with studies mostly focusing on ultrasonic and infrasonic vibrations. In the audible range (20 Hz to 20 kHz), sound has been shown to both increase colony formation and disrupt microbial growth, depending upon the organism and frequency of sound used. In the brewer's yeast , sound has been shown to significantly alter growth, increase alcohol production, and affect the metabolite profile. In this study, was exposed to a continuous 90 dB @ 20 μPa tone at different frequencies (0.1 kHz, 10 kHz, and silence). Fermentation characteristics were monitored over a 50-h fermentation in liquid malt extract, with a focus on growth rate and biomass yield. The profile of volatile metabolites at the subsequent stationary phase of the ferment was characterised by headspace gas chromatography-mass spectrometry. Sound treatments resulted in a 23% increase in growth rate compared to that of silence. Subsequent analysis showed significant differences in the volatilomes between all experimental conditions. Specifically, aroma compounds associated with citrus notes were upregulated with the application of sound. Furthermore, there was a pronounced difference in the metabolites produced in high- versus low-frequency sounds. This suggests industrial processes, such as beer brewing, could be modulated by the application of audible sound at specific frequencies during growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo11090605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468475PMC
September 2021

Vascular smooth muscle cell dysfunction contribute to neuroinflammation and Tau hyperphosphorylation in Alzheimer disease.

iScience 2021 Sep 19;24(9):102993. Epub 2021 Aug 19.

Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Boston, MA 02114, USA.

Despite the emerging evidence implying early vascular contributions to neurodegenerative syndromes, the role of vascular smooth muscle cells (VSMCs) in the pathogenesis of Alzheimer disease (AD) is still not well understood. Herein, we show that VSMCs in brains of patients with AD and animal models of the disease are deficient in multiple VSMC contractile markers which correlated with Tau accumulation in brain arterioles. and experiments demonstrated that VSMCs undergo dramatic phenotypic transitions under AD-like conditions, adopting pro-inflammatory phenotypes. Notably, these changes coincided with Tau hyperphosphorylation at residues Y18, T205, and S262. We also observed that VSMC dysfunction occurred in an age-dependent manner and that expression of Sm22α protein was inversely correlated with CD68 and Tau expression in brain arterioles of the 3xTg-AD and 5xFAD mice. Together, these findings further support the contribution of dysfunctional VSMCs in AD pathogenesis and nominate VSMCs as a potential therapeutic target in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2021.102993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417400PMC
September 2021
-->