Cytosolic DNA fragments represent pathogen and danger associated molecular patterns and induces a cascade of innate immune responses in the cells. Excessive cytosolic DNA can enhance chronic inflammation predominantly by activating inflammasomes therefore contributing to the pathogenesis of chronic diseases such as psoriasis. Psoriasis associated non-protein coding RNA induced by stress (PRINS) is a long non-coding RNA, which has already been associated with psoriasis susceptibility and cellular stress response; however its precise mechanism was less studied. The aim of this study was to identify the role of PRINS in psoriasis associated inflammatory reactions, which could explain the importance of its high expression in psoriatic uninvolved epidermis. The synthetic DNA analogue poly(dA:dT) transfection was used to induce inflammatory reactions in normal human epidermal keratinocytes (NHEKs), and expression of inflammatory cytokines was measured by real-time RT-PCR and ELISA. Poly(dA:dT) transfection induced the expression and secretion of IL-1a, IL-1b, IL-6 and TNF-a, while decreased PRINS expression was detected. To study the possible role of PRINS in the poly(dA:dT) induced cytokine production of NHEKs we forced its expression by vector based method. Overexpression of PRINS reduced the poly(dA:dT)-induced IL-6 production, but did not affect the production of the other investigated cytokines. In silico analysis revealed a putative interaction site between PRINS and the mRNA of IL-6 and the interaction was confirmed by an in vitro binding assay. On cellular level, destruction of the IL-6 mRNA binding site in the PRINS sequence lead to the loss of PRINS' ability to inhibit IL-6 production. These results show a restrictive effect of PRINS in inflammatory processes, and indicate the role of its higher expression in psoriatic uninvolved epidermis.
Seoul-t'ukpyolsi, Republic of Korea Here we investigated effects of anacardic acid (AA) on the regulation of lipogenesis in differentiated human adipocytes, and elucidated possible epigenetic mechanisms via p300 histone acetyltransferase activity. To investigate the role of histone acetylation in lipogenesis regulation, we evaluated triglyceride (TG) contents, expression of key lipogenic enzyme acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c) in primary cultured adipocytes isolated from subcutaneous adipose tissues. Treatment of AA or knockdown of p300 by using transient transfection of p300 siRNA led to significant reduction of TG contents, SREBP-1c and ACC expression, indicating that p300 mediates SREBP-1, ACC expression, and corollary lipid production. While p300 overexpression by p300WT was associated with significantly enhanced activity of SREBP1-908luc promoter, the SREBP1-908luc promoter activity was significantly reduced in the presence of p300DHAT. In addition, we performed a promoter assay using HEK293T cells treated with AA or TSA. While the SREBP1-908luc promoter activity was significantly decreased by AA, but significantly increased by TSA treatment. These findings suggest that histone acetyltransferase activity of p300, not a p300 expression per se, is critical for the transcriptional regulation of SREBP-1 and p300HAT inhibitors such as AA could be employed as anti-obesity modalities.
Objectives: Few studies have attempted to quantify the costs of operating room (OR) time. The purpose of this study is to quantify the variable cost per OR minute in isolated non-robotic valvular procedures -aortic valve replacement (AVR), mitral valve replacement (MVR), and mitral valve repair (MVRepair). MethOds:The Premier database, one of the most comprehensive hospital databases, was queried from 2007 to 2011 for patients undergoing AVR, MVR, or MVRepair. This database contains complete billing, hospital cost, and coding data from > 600 US facilities. Patients were identified using the following International Classification of Diseases 9 th Revision (ICD-9) procedure codes: AVR 35. 21, 35.22; MVR 35.23, 35.24; and MVRepair 35.12. Patients having coronary artery bypass grafting were excluded. The surgical approaches, right thoracotomy (RT) and any sternal incision, were identified for each patient with expert clinical assistance. Patients with right thoracotomy were then propensity score matched to patients with any sternal incision, adjusting for patient differences. Premier classified variable costs of the OR into three categories; staff for the surgery room, anesthesia, and recovery room. Outliers were identified based on the cost per minute of the procedure. The top and bottom five percent were removed. All costs were adjusted to 2012 dollars using the Medical Care Component of the Consumer Price Index. Results: There were 2,657 valvular procedures -1,604 AVR, 434 MVR, and 619 MVRepair -that met the inclusion criteria. The average cost per OR minute
High mobility group box 1" (HMGB1) is a well-known nuclear protein that stabilizes DNA and facilitates gene transcription, but at outside the membrane, it functions as an alarmin, causing an inflammatory response in combination with other cytokines. Recently, we confirmed that HMGB1 shows the proinflammatory activity depending on the redox status, which is in the reduced, disulfide, or oxidized form. The reduced-HMGB1 exerts a chemoattractive effect, and the disulfide-HMGB1 has proinflammatory cytokine activity, but the oxidized form has no inflammatory activity. In our previous study, the proinflammatory effect of disulfide-HMGB1 was seen under the poly(I:C)-induced inflammation in keratinocyte, but reduced-HMGB1 showed the suppressive effect of poly(I:C)-induced inflammation. In addition, HMGB1 contains two homologous DNA-binding domains, the A and B-boxes. HMGB1 B-box induces strong proinflammatory activities, but HMGB1 A-box is a specific antagonist for HMGB1 and exerts an anti-inflammatory effect in macrophage. However, the direct effects of HMGB1 A-box and B-box for keratinocytes were not well elucidated. To investigate those effects, we established recombinant peptides for HMGB1 A-box and B-box. HMGB1 A and B-box alone did not induce inflammatory cytokines for keratinocyte on own. On the other hand, HMGB1 A-box had suppressive effect for IL-6 and IFN-beta expression on poly (I:C) induced inflammation in keratinocyte, but HMGB1 B-box had no inflammatory in keratinocytes. From these results, it is possible that HMGB1 A-box could become a new antiinflammatory material for some inflammatory skin diseases.
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