Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor beta

Understanding the impact of extracellular matrix sub-types and mechanical stretch on cardiac fibroblast activity is required to help unravel the pathophysiology of myocardial fibrotic diseases. Therefore, the purpose of this study was to investigate pro-fibrotic responses of primary human cardiac fibroblast cells exposed to different extracellular matrix components, including collagen sub-types I, III, IV, VI and laminin. The impact of mechanical cyclical stretch and treatment with transforming growth factor beta 1 (TGFβ1) on collagen 1, collagen 3 and alpha smooth muscle actin mRNA expression on different matrices was assessed using quantitative real-time PCR. Our results revealed that all of the matrices studied not only affected the expression of pro-fibrotic genes in primary human cardiac fibroblast cells at rest but also affected their response to TGFβ1. In addition, differential cellular responses to mechanical cyclical stretch were observed depending on the type of matrix the cells were adhered to. These findings may give insight into the impact of selective pathological deposition of extracellular matrix proteins within different disease states and how these could impact the fibrotic environment.

Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica indicates reduced metabolism and immune responses

Schistosomiasis is a significant cause of human morbidity and mortality. We performed a genome-wide transcriptional survey of liver biopsies obtained from Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis with a current or past history of viral hepatitis B. Both disease groups were compared with patients with no prior history or indicators of any liver disease. Analysis showed in the main, downregulation in gene expression, particularly those involved in signal transduction via EIF2 signalling and mTOR signalling, as were genes associated with cellular remodelling. Focusing on immune associated pathways, genes were generally downregulated. However, a set of three genes associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential gene profiles unique to schistosomiasis included the gene Granulin which was decreased despite being generally considered a marker for liver disease, and IGBP2 which is associated with increased liver size, and was the most upregulated gene in schistosomiasis only patients, all of which presented with hepatomegaly. The unique features of gene expression, in conjunction with previous reports in the murine model of the cellular composition of granulomas, granuloma formation and recovery, provide an increased understanding of the molecular immunopathology and general physiological processes underlying hepatic schistosomiasis.

Informal caregiving and mental ill health – differential relationships by workload, gender, age and area-remoteness in a UK region

Informal caregiving can be a demanding role which has been shown to impact on physical, psychological and social wellbeing. Methodological weaknesses including small sample sizes and subjective measures of mental health have led to inconclusive evidence about the relationship between informal caregiving and mental health. This paper reports on a study carried out in a UK region which investigated the relationship between informal caregiving and mental ill health. The analysis was conducted by linking three datasets, the Northern Ireland Longitudinal Study, the Northern Ireland Enhanced Prescribing Database and the Proximity to Service Index from the Northern Ireland Statistics and Research Agency. Our analysis used both a subjective measure of mental ill health, i.e. a question asked in the 2011 Census, and an objective measure, whether the respondents had been prescribed antidepressants by a General Practitioner between 2010 and 2012. We applied binary logistic multilevel modelling to these two responses to test whether, and for what sub-groups of the population, informal caregiving was related to mental ill health. The results showed that informal caregiving per se was not related to mental ill health although there was a strong relationship between the intensity of the caregiving role and mental ill health. Females under 50, who provided over 19 hours of care, were not employed or worked part-time and who provided care in both 2001 and 2011 were at a statistically significantly elevated risk of mental ill health. Caregivers in remote areas with limited access to shops and services were also at a significantly increased risk as evidenced by prescription rates for antidepressants. With community care policies aimed at supporting people to remain at home, the paper highlights the need for further research in order to target resources appropriately.