Plos One
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The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. ⋯ Pathological and histological analyses revealed mitigation of the inflammatory response and reduced cell infiltration in the peritoneal tissue surrounding the implants after baicalin treatment. Measurement of the cytokine levels in the peritoneal lavage fluid of mice in the baicalin treatment group revealed a decrease in IL-4, an increase in interferon γ (IFN-γ), and a reversed IFN-γ/IL-4 ratio compared with the control group, indicating that baicalin treatment activated the Th1-induced immune response to expedite bacterial load clearance. Based on these results, baicalin might be a potent QS inhibitor and anti-biofilm agent for combating Pseudomonas aeruginosa biofilm-related infections.
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Accurate measurement of physical performance in individuals with musculoskeletal pain is essential. Accelerometry is a powerful tool for this purpose, yet the current methods designed to evaluate energy expenditure are not optimized for this population. The goal of this study is to empirically derive a method of accelerometry analysis specifically for musculoskeletal pain populations. ⋯ These new accelerometry intervals provide a model for objective measurement of real-life physical performance in people with pain and musculoskeletal disorders, with many potential uses. They may be used to better evaluate the relationship between pain and daily physical function, monitor musculoskeletal disease progression, gauge disease severity, inform exercise prescription, and quantify the functional impact of treatments. Based on these findings, we recommend that future studies of pain and musculoskeletal disorders analyze accelerometry output based on these new "physical performance" intervals.
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In an effort to make affordable vaccines suitable for the regions most affected by HIV-1, we have constructed stable vaccines that express an HIV-1 subtype C mosaic Gag immunogen (BCG-GagM, MVA-GagM and DNA-GagM). Mosaic immunogens have been designed to address the tremendous diversity of this virus. Here we have shown that GagM buds from cells infected and transfected with MVA-GagM and DNA-GagM respectively and forms virus-like particles. ⋯ Similarly, DNA-GagM vaccination generated 7-fold higher levels of cytokine-positive CD8+ T cells than DNA-GagN, indicating that this subtype C mosaic Gag elicits far more potent immune responses than a consensus-type Gag. Cells transfected and infected with DNA-GagM and MVA-GagM respectively, expressed high levels of GagM and produced budding virus-like particles. Our data indicates that a heterologous prime boost regimen using DNA and MVA vaccines expressing HIV-1 subtype C mosaic Gag is highly immunogenic in mice and warrants further investigation in non-human primates.
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Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. ⋯ In the central nervous system, PTX induced significant astrocyte activation in the spinal cord dorsal horn, and both PTX and OXA caused reduction of P2ry12+ homeostatic microglia, with no measurable changes in IBA-1+ microglia/macrophages in the dorsal and ventral horns. We also found that PTX induced up-regulation of several inflammatory cytokines and chemokines (TNF-α, IFN-γ, CCL11, CCL4, CCL3, IL-12p70 and GM-CSF) in the spinal cord. Overall, these findings suggest that PTX and OXA cause distinct pathological changes in the periphery and nervous system, which may contribute to chemotherapy-induced neuropathic pain.
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Chronic inflammation and oxidative stress are striking features of Duchenne muscular dystrophy disease. Diacerhein is an anthraquinone, which exhibits anti-inflammatory and antioxidant properties. Based on their actions, the present study evaluated the effects of diacerhein against myonecrosis, oxidative stress and inflammatory response in the diaphragm muscle of mdx mice and compared these results to current treatment widely used in DMD patients, with a main focus on the impact of prednisone. ⋯ Regarding oxidative stress, diacerhein treatment was effective in reducing the ROS and lipid peroxidation in the diaphragm muscle from mdx mice. Compared to prednisone treatment, our findings demonstrated that diacerhein treatment improved the dystrophic phenotype in the diaphragm muscle of mdx mice similar to that of glucocorticoid therapy. In this respect, this work suggests that diacerhein has a potential use as an alternative drug in dystrophinopathy treatment and recommends that its anti-inflammatory and antioxidants properties in the dystrophic muscle should be better understood.