Versican, a chondroitin sulphate proteoglycan, is one of the key components of the provisional extracellular matrix expressed after injury. The current study evaluated the hypothesis that a ...versican-rich matrix alters the phenotype of cultured fibroblasts.
The full-length cDNA for the V1 isoform of human versican was cloned and the recombinant proteoglycan was expressed in murine fibroblasts. Versican expression induced a marked change in fibroblast phenotype. Functionally, the versican-expressing fibroblasts proliferated faster and displayed enhanced cell adhesion, but migrated slower than control cells. These changes in cell function were associated with greater N-cadherin and integrin β1 expression, along with increased FAK phosphorylation. The versican-expressing fibroblasts also displayed expression of smooth muscle α-actin, a marker of myofibroblast differentiation. Consistent with this observation, the versican fibroblasts displayed increased synthetic activity, as measured by collagen III mRNA expression, as well as a greater capacity to contract a collagen lattice. These changes appear to be mediated, at least in part, by an increase in active TGF-β signaling in the versican expressing fibroblasts, and this was measured by phosphorylation and nuclear accumulation of SMAD2.
Collectively, these data indicate versican expression induces a myofibroblast-like phenotype in cultured fibroblasts.
Leprosy, caused by infection with Mycobacterium leprae or the recently discovered Mycobacterium lepromatosis, was once endemic in humans in the British Isles. Red squirrels in Great Britain (Sciurus ...vulgaris) have increasingly been observed with leprosy-like lesions on the head and limbs. Using genomics, histopathology, and serology, we found M. lepromatosis in squirrels from England, Ireland, and Scotland, and M. leprae in squirrels from Brownsea Island, England. Infection was detected in overtly diseased and seemingly healthy animals. Phylogenetic comparisons of British and Irish M. lepromatosis with two Mexican strains from humans show that they diverged from a common ancestor around 27,000 years ago, whereas the M. leprae strain is closest to one that circulated in Medieval England. Red squirrels are thus a reservoir for leprosy in the British Isles.
The overhunting of wildlife for food and commercial gain presents a major threat to biodiversity in tropical forests and poses health risks to humans from contact with wild animals. Using a recent ...survey of wildlife offered at wild meat markets in Malaysia as a basis, we review the literature to determine the potential zoonotic infection risks from hunting, butchering and consuming the species offered. We also determine which taxa potentially host the highest number of pathogens and discuss the significant disease risks from traded wildlife, considering how cultural practices influence zoonotic transmission. We identify 51 zoonotic pathogens (16 viruses, 19 bacteria and 16 parasites) potentially hosted by wildlife and describe the human health risks. The
Suidae
and the
Cervidae
families potentially host the highest number of pathogens. We conclude that there are substantial gaps in our knowledge of zoonotic pathogens and recommend performing microbial food safety risk assessments to assess the hazards of wild meat consumption. Overall, there may be considerable zoonotic risks to people involved in the hunting, butchering or consumption of wild meat in Southeast Asia, and these should be considered in public health strategies.
Abstract The concept of the involvement of inflammation in the pathogenesis of atherosclerosis has existed since the 1800s, stemming from sentinel pathologic observations made by Rudolf Virchow, Karl ...Rokitansky, and others. Our understanding of the complex role played by immune and inflammatory mediators in the initiation and progression of atherosclerosis has evolved considerably in the intervening years, and today, a dramatically evolved understanding of these processes has led to advances in both diagnostic and prognostic approaches, as well as novel treatment modalities targeting inflammatory and immune mediators. Therapeutic interventions working through multiple mechanisms involved in atheroma pathogenesis, such as statins, which both lower lipids and alter the inflammatory milieu in the vessel wall, hold promise for the future. In this brief review, we explore the biological role of inflammation in atherosclerosis, with a focus on cellular involvement in both acute and chronic inflammation, and outline novel biomarkers of inflammation and atherosclerosis with a particular focus on the potential application of these novel approaches in improving strategies for disease diagnosis and management.
Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis ...in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D3) and cardiac fibrosis in human myocardial samples.
Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation.
Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis.
Canine adenovirus type 1 (CAV-1) causes infectious canine hepatitis (ICH), a frequently fatal disease which primarily affects canids. In this study, serology (ELISA) and molecular techniques ...(PCR/qPCR) were utilised to investigate the exposure of free-ranging red foxes (Vulpes vulpes) to CAV-1 in the United Kingdom (UK) and to examine their role as a wildlife reservoir of infection for susceptible species. The role of canine adenovirus type 2 (CAV-2), primarily a respiratory pathogen, was also explored. In foxes with no evidence of ICH on post-mortem examination, 29 of 154 (18.8%) red foxes had inapparent infections with CAV-1, as detected by a nested PCR, in a range of samples, including liver, kidney, spleen, brain, and lung. CAV-1 was detected in the urine of three red foxes with inapparent infections. It was estimated that 302 of 469 (64.4%) red foxes were seropositive for canine adenovirus (CAV) by ELISA. CAV-2 was not detected by PCR in any red foxes examined. Additional sequence data were obtained from CAV-1 positive samples, revealing regional variations in CAV-1 sequences. It is concluded that CAV-1 is endemic in free-ranging red foxes in the UK and that many foxes have inapparent infections in a range of tissues.
Vitamin D in Heart Failure Meredith, Anna J., BSc; McManus, Bruce M., MD, PhD, FRSC
Journal of cardiac failure,
10/2013, Letnik:
19, Številka:
10
Journal Article
Recenzirano
Abstract Evidence linking vitamin D to cardiovascular (CV) health has accumulated in recent years: numerous epidemiologic studies report deficiency as a significant CV risk factor, and rodent models ...suggest that active vitamin D can modulate critical remodeling processes, including cardiac hypertrophy and extracellular matrix remodeling. The presence of vitamin D signaling machinery within the human heart implies a direct role for this hormone in cardiac physiology and may explain associations between vitamin D status and CV outcomes. Heart failure (HF) represents a growing social and economic burden worldwide. Myocardial remodeling is central to HF development, and in the context of emerging evidence supporting mechanistic involvement of vitamin D, this review provides critical appraisal of scientific literature related to the role of vitamin D in CV disease, including data from epidemiologic and supplementation studies, as well as novel findings from animal models and in vitro work. Although associative data linking vitamin D and CV outcomes and evidence supporting a role for vitamin D in relevant pathogenic processes are both substantial, there are limited mechanistic data to indicate vitamin D supplementation as a viable therapeutic adjunct for the prevention of HF development following myocardial injury.
Hybridisation between wild and domestic species poses a serious challenge to conservation management and can, potentially, lead to extinction. Alongside it, disease transmission will inevitably ...occur. However, the link between these two phenomena has historically been neglected. In Scotland, the European wildcat is particularly threatened by hybridisation with the domestic cat, a process promoted by long-term habitat loss, human encroachment, and persecution. Between 2015 and 2019, free-living cats (n = 120) were captured in six conservation priority areas of northern Scotland. Samples were collected for infectious disease screening (feline immunodeficiency virus, feline leukaemia virus, feline calicivirus, feline herpesvirus, Chlamydia felis, Mycoplasma felis, Bordetella bronchiseptica, Mycoplasma haemofelis, Candidatus Mycoplasma haemominutum, Candidatus Mycoplasma turicensis, and Tritrichomonas foetus) and genetic analysis. Polymerase chain reaction and reverse transcriptionPCR were used to detect infectious DNA or RNA, respectively. The hybrid score (Q) for each individual cat was determined using a 35-SNP-marker test. Statistical analysis investigated the association between Q and probability of infection, accounting for spatial clustering. The results confirmed the presence of 11 infectious agents circulating in the free-living cat population of northern Scotland, which consists of a hybrid swarm between F. silvestris and F. catus. For eight of them (feline leukaemia virus, feline herpesvirus C. felis, B. bronchiseptica, M. felis, M. haemofelis, Ca. M. haemominutum, and T. foetus), there was no significant association between infection probability and Q, supporting our hypothesis that the hybrid swarm may be functioning as a single epidemiological unit. Considering the impact of infectious diseases on health, welfare, and population dynamics of domestic cats, their presence in the extremely fragile and hybridised population of F. silvestris in Scotland could be population limiting or, potentially, contribute to local extinction. Comprehensive disease surveillance, risk analysis, and domestic cat management will be essential for the European wildcat conservation, particularly where hybridisation is increasing and anthropogenic factors are prevalent.
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