Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti-inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)-induced ALI. The results demonstrated that a vitamin D agonist, calcitriol, exhibited a beneficial effect on LPS-induced ALI in rats; calcitriol pretreatment significantly improved LPS-induced lung permeability, as determined using Evans blue dye. Results from reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA analysis demonstrated that calcitriol also modulated the expression of members of the renin-angiotensin system (RAS), including angiotensin (Ang) I-converting enzymes (ACE and ACE2), renin and Ang II, which indicates that calcitriol may exert protective effects on LPS-induced lung injury, at least partially, by regulating the balance between the expression of members of the RAS. The results of the present study may provide novel targets for the future treatment of ALI.
Objective. RNA interference is a process in which genes can be silenced sequence-specifically. In mammals, RNA interference can be invoked by introduction of small (19-21-nucleotide) double-stranded RNA molecules known as small interfering RNA (siRNA) into cells. Thereby, siRNA offers promise as a novel therapeutic modality. However, siRNA is a relatively large, highly charged molecule and does not readily enter cells. This study was undertaken to investigate the use of electroporation for in vivo transfection of siRNA into joint tissue in arthritic mice to achieve local RNA interference.Methods. Proof of principle that siRNA is able to inhibit gene expression in vivo in the mouse joint was studied by local injection and electroporation of siRNA designed to silence reporter genes. In mice with collagen-induced arthritis (CIA), the diseasemodulating activity of siRNA designed to silence tumor necrosis factor ␣ (TNF␣) was investigated.Results. Luciferase activity could be reduced by >90% with luciferase-specific siRNA as compared with the activity measured after electroporation without siRNA or with irrelevant siRNA. The effect was observed only locally. In mice with CIA, electroporation of siRNA designed to inhibit TNF␣ strongly inhibited joint inflammation, whereas electroporation of irrelevant siRNA or injection of siRNA against TNF␣ without electroporation failed to produce therapeutic effects.Conclusion. Local electroporation of siRNA in joint tissue can inhibit CIA in mice. These results offer promise for the use of siRNA as a new strategy for therapeutic intervention in rheumatoid arthritis and may serve as a tool to study arthritis disease pathways through loss-of-function phenotypes.
Conductive hydrogels have emerged as promising material candidates for multifunctional strain sensors attributing to their similarity to biological tissues, good wearability, and high accuracy of information acquisition. However, it is...
Airborne particulate matter (PM) is causing more and more serious air pollution and threatening the public health. However, existing air filter technologies with the easy-to-block manner can rarely meet the requirements of high-performance PM filters. Here we propose a conceptually new type of inertial impaction filters for rapidly high-efficiency PM removal. Under the airflow velocity of 8.0 m/s, the real inertial impaction filters show high PM removal efficiencies of up to 97.77 ± 1.53% and 99.47 ± 0.45% for PM2.5 and PM10, respectively. Compared with the traditional air filters reported previously, the inertia impaction filters exhibit extremely low pressure drop of 5–10 Pa and high quality factor (QF) values of 0.380 Pa−1 and 0.524 Pa−1 for PM2.5 and PM10, respectively. These greatly improved QF values are achieved through a series of inertial separation processes. The feature dimension of filtration channel is dozens of times larger than PM average size, which greatly decreases airflow resistance. Particularly, this inertial structure can be made of various types of materials, which shows great potential for low-cost fabrication of large-area devices. As a stand-alone device or incorporated with the existing PM air filter, this inertial impaction filter will bring great benefits to the public health.
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