James Pritchett

Manchester Metropolitan University | MMU · Centre for Bioscience

Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in und...

Fibrosis due to extracellular matrix (ECM) secretion from myofibroblasts complicates many chronic liver diseases causing scarring and organ failure. Integrin-dependent interaction with scar ECM promotes pro-fibrotic features. However, the pathological intracellular mechanism in liver myofibroblasts is not completely understood, and further insight...

Unlabelled: Osteopontin (OPN) is an important component of the extracellular matrix (ECM), which promotes liver fibrosis and has been described as a biomarker for its severity. Previously, we have demonstrated that Sex-determining region Y-box 9 (SOX9) is ectopically expressed during activation of hepatic stellate cells (HSC) when it is responsibl...

The transcription factor SOX9 is crucial for multiple aspects of development. Mutations in SOX9 cause campomelic dysplasia, a haploinsufficiency disorder concordant with the expression profile of SOX9 during embryogenesis. The mechanistic understanding of development has revealed roles for SOX9 in regulating cartilage extracellular matrix (ECM) pro...

Stromal derived factor (SDF-1), an alpha chemokine, is a widely known chemoattractant in the immune system. A growing body of evidence now suggests multiple regulatory roles for SDF-1 in the developing nervous system. To investigate the role of SDF-1 signaling in the growth and differentiation of cortical cells, we performed numerous in vitro exper...

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an e...

Myofibroblasts are responsible for scarring and organ stiffness during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state linked to an increasingly pro-fibrotic phenotype. Here, we have discovered mechanical stress from progressive scarring induces nuclear softening and de-repression of he...

Background The aim of this study was to investigate for links between reported pain and inflammation within a sub-cohort of patients undergoing the IPOM plus repair through the measurement of serum/plasma levels of established inflammatory biomarkers in trial participants across 1-year follow up. Methods 22 patients (12 Protack™ and 10 Reliatack™)...

Background A study examining post-op pain, comparing permanent versus absorbable tack fixation devices, Protack™ versus Reliatack™, in IPOM plus repair. Methods TACKoMesh is a single-centre double-blind RCT conducted from 2017–2020 with 1-year follow up. Patients were randomised to either Protack™ (titanium tacks) or Reliatack™ (an articulating-ar...

Background The aim of this study was to determine the temporal evolution of extracellular matrix (ECM) remodelling and collagen biomarkers and their influence on incisional hernia recurrence after the IPOM plus repair. Methods A sub-cohort of patients (n=25) undergoing laparoscopic incisional hernia repair within the TACKoMesh randomised controlle...

Access to safe drinking water free from microbial pollution is an issue of global concern. The use of photocatalytic thin films in water treatment has focused on titanium dioxide, which requires UV-activation, proving a potential barrier to upscaling and implementation in the real world. Visible-light-activated photocatalytic thin films, such as bi...

Renal fibrosis is a common end point for kidney injury and many chronic kidney diseases. Fibrogenesis depends on the sustained activation of myofibroblasts, which deposit the extracellular matrix that causes progressive scarring and organ failure. Here, we showed that the transcription factor SOX9 was associated with kidney fibrosis in humans and r...

Background Surgery to the abdominal wall is ubiquitous worldwide and hernia treatment is challenging and expensive, posing a critical need to tailor treatment to individual patient risk-factors. In this systematic review, we consider specific systemic factors with potential as biomarkers of hernia formation. Methods A healthcare database-assisted...

Introduction Liver fibrosis is excessive remodelling of the extracellular matrix (ECM) leading to tissue scarring and eventually impaired liver function. Hepatic stellate cells (HSCs) are the key cellular drivers of liver fibrosis responsible for the formation of stiffened fibrotic ECM in response to liver injury. Activation of HSCs is driven and m...

BACKGROUND Plain language summaries (PLS) are intended to provide readers with a clear, non-technical, and easily understandable overview of medical and scientific literature; however, audience preferences for specific PLS format have yet to be fully explored. OBJECTIVE To evaluate the preferred readability level and format for PLS of medical jour...

Background: Plain language summaries (PLSs) are intended to provide readers with a clear, nontechnical, and easily understandable overview of medical and scientific literature; however, audience preferences for specific PLS formats have yet to be fully explored. Objective: This study aims to evaluate the preferred readability level and format fo...

Liver sinusoidal endothelial cells (LSECs) are specialized endothelial cells that have essential roles in normal liver homeostasis, and are also involved in disease processes. The importance of LSEC biology has recently been extensively reviewed (1, 2). LSECs line the walls of the hepatic sinusoid (Figure 1) where they scavenge blood borne macromol...

Renal fibrosis is a common endpoint for many chronic kidney diseases. Extracellular matrix (ECM) from myofibroblasts causes progressive scarring and organ failure. The mechanisms underlying fibrogenesis and how it is sustained are incompletely understood. Here, we show that the transcription factor, Sex determining region Y-box 9 (SOX9), is require...

Extracellular matrix (ECM) deposition and resultant scar play a major role in the pathogenesis and progression of liver fibrosis. Identifying core regulators of ECM deposition may lead to urgently needed diagnostic and therapetic strategies for the disease. The transcription factor Sex determining region Y box 9 (SOX9) is actively involved in scar...

The insertion of prosthetic devices into the oral cavity affects the oral microflora and results in accumulation of microorganisms on the prosthetic surface. Such fouling of denture surfaces can lead to a number of oral diseases and consequently to the replacement of the denture. Here, we report the post-synthesis introduction of silver in zeolite-...

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Supplementary Figures 1-14 and Supplementary Tables 1 & 2.

Background and Aims Liver fibrosis is a major cause of morbidity and mortality. It is characterised by excessive extracellular matrix (ECM) deposition from activated hepatic stellate cells (HSCs). Although potentially reversible, treatment remains limited. Understanding how ECM influences the pathogenesis of the disease may provide insight into nov...

Introduction Fibrosis of the liver is characterised by progressive accumulation of extracellular matrix (ECM) proteins and is a major cause of morbidity and mortality in the UK. Several cell-types are responsible for this, but a major role is played by activation of the hepatic stellate cell (HSC). We have identified ectopic expression of the Sry-b...

Vasoconstrictors activate phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP(2)), leading to calcium mobilization, protein kinase C activation, and contraction. Our aim was to investigate whether PLC-delta(1), a PLC isoform implicated in alpha(1)-adrenoreceptor signaling and the pathogenesis of hypertension, is invol...

Stromal-derived factor 1 (SDF-1), a known chemoattractant, and its receptor CXCR4 are widely expressed in the developing and adult cerebral cortex. Recent studies have highlighted potential roles for SDF-1 during early cortical development. In view of the current findings, our histological analysis has revealed a distinct pattern of SDF-1 expressio...

Characterization of E15 wild type and CXCR4-/- brain sections. Labeling of wild type (a-c) and mutant cortex (a'-c') for Ki67 (a, a'), MAP2 (b, b') and GABA (c, c') immunoreactivity; arrows in c, c' indicate GABA immunostaining in the MZ. (d) Line-scan analysis of mutant and wild type sections stained for Ki67. Because the pattern of staining was r...

We have investigated serum chemokines for their suitability as markers of atherosclerosis development in apoE (apolipoprotein E)-deficient ((-/-)) mice. Female C3H apoE(-/-) and C57BL apoE(-/-) mice were fed on either diet W (Western diet; 6 weeks) or normal rodent diet (12 weeks). Serum lipids (0, 6 and 12 weeks) and terminal chemokine levels were...