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Our results clearly support an immunopathological role for neutrophils by mediating tissue destruction, which resulted in significant early mortality.
As well as mediating tissue destruction, RASFs play a major role in catalyzing and sustaining RA by producing inflammatory cytokines such as interleukin-1-beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), proangiogenic factors, and matrix-degrading enzymes [ 1, 2].
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TUNEL staining in these mice appears confluent, especially around blood vessels and highlighting large foci of necrotic infiltrates that have been shown to be rich sources of damage associated molecular patterns (DAMPs) that can potentially further exacerbate host mediated tissue destruction [14], [17].
Serine protease inhibitors such as SLPI act locally to maintain a protease/antiprotease balance thereby preventing protease mediated tissue destruction [ 7].
The SLPI has previously been reported to be upregulated in arthritic joints and to mediate tissue destruction and inflammation in a rat model of arthritis induced by intraperitoneal injection of SCW [ 26].
Neutrophils are also believed to be the more important for the development of chronic obstructive pulmonary disease (COPD), because of their ability to release elastase which mediates tissue destruction [ 46].
RA-FLSs not only mediate tissue destruction but also are considered to play a major role in initiating and driving RA in concert with inflammatory cells [ 7].
Interestingly, a polymorphism in the 3'-UTR of the miR-146a target gene was recently shown to be associated with RA susceptibility [ 86]. miR-155 overexpression in synovial fibroblasts was able to prevent the TLR and cytokine-inducible expression of specific matrix metalloproteinases that mediate tissue destruction in RA [ 81].
TH-17 cells produce IL-17, which coordinates tissue inflammation by inducing inflammatory cytokines, chemokines and matrix metalloproteinases capable of mediating tissue infiltration and destruction.
Selective eradication of cells involved in pathological activities, such as cancer cells or cells mediating inflammatory tissue destruction, is a major challenge for modern medicine.
It is involved in the defense against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in aggressive and chronic periodontitis.
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