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New Findings: What is the central question of this study?Peritoneal injury can result in a persistent fibroproliferative process in the abdominal cavity, causing pain and loss of function of internal organs. This study aimed to demonstrate the use of sodium butyrate (NaBu) as a potential agent to attenuate peritoneal fibrosis induced by a synthetic matrix.What is the main finding and its importance?Our findings provide the first evidence that NaBu attenuates the inflammatory, angiogenesis and fibrogenesis axes involved in the formation of peritoneal fibrovascular tissue, indicating the potential of this compound to ameliorate peritoneal fibrosis. The aim of this study was to identify the bio‐efficacy of sodium butyrate (NaBu) on preventing the development of peritoneal fibrovascular tissue induced by implantation of a synthetic matrix in the abdominal cavity. Polyether–polyurethane sponge discs were implanted in the peritoneal cavity of mice, which were treated daily with oral administration of NaBu (100 mg/kg). Control animals received water (100 μl). After 7 days, the implants were removed for assessment of inflammatory, angiogenic and fibrogenic markers. Compared with control values, NaBu treatment decreased mast cell recruitment/activation, inflammatory enzyme activities, levels of pro‐inflammatory cytokines, and the proteins p65 and p50 of the nuclear factor‐κB pathway. Angiogenesis, as determined by haemoglobin content, vascular endothelial growth factor levels and the number of blood vessels in the implant, was reduced by the treatment. In NaBu‐treated animals, the predominant collagen present in the abdominal fibrovascular tissue was thin collagen, whereas in control implants it was thick collagen. Transforming growth factor‐β1 levels were also lower in implants of treated animals. Sodium butyrate downregulated the inflammatory, angiogenesis and fibrogenesis axes of the fibroproliferative tissue induced by the intraperitoneal synthetic matrix. This compound has potential to control/regulate chronic inflammation and adverse healing processes in the abdominal cavity. [ABSTRACT FROM AUTHOR]

A number of genetic factors have been linked to the development of diabetes, a condition that often requires implantable devices such as glucose sensors. In normoglycaemic individuals, this procedure induces a foreign body reaction (FBR) that is detrimental to bioimplant functionality. However, the influence of the genetic background on this reaction in diabetes has not been investigated. We examined the components of FBR (capsule thickness, collagen deposition, mast cell and foreign body giant cell number) in subcutaneous implants of polyether polyurethane (SIPP) in streptozotocin (STZ)‐induced diabetes in Swiss, C57BL/6 and Balb/c mice. The fasting blood glucose levels before STZ injections were 133.5 ± 5.1 mg/dL, after the treatment increased 68.4% in Swiss mice, 62.4% in C57BL/6 and 30.9% in Balb/c mice. All FBR features were higher in implants of Swiss and C57BL/6 mice compared with those in implants of Balb/c. Likewise, the apoptotic index was higher in implants of diabetic Swiss and C57BL/6 mice whose glycaemic levels were the highest. Our findings show an association between the severity of hyperglycaemic levels and the intensity of the FBR to SIPP. These important strain‐related differences in susceptibility to diabetes and the intensity of the FBR must be considered in management using implantable devices in diabetic individuals. [ABSTRACT FROM AUTHOR]

Natriuretic peptide receptor-C activation by the synthetic ligand C- ANP-4-23, a specific agonist for this receptor, has been shown to inhibit key events of the angiogenic cascade, such as migration, proliferation and vascular endothelial growth factor ( VEGF) production. In the present study we investigated whether C- ANP4-23 could also inhibit angiogenesis in the sponge model in vivo. To this end, we evaluated the effects of C- ANP4-23 on inflammatory and angiogenic components of the fibrovascular tissue induced by polyether polyurethane sponge implants in mice. Measurements of the haemoglobin content ( μg/mg wet tissue) and blood flow (laser Doppler perfusion imaging) of the implants, used as an index of vascularization, revealed that single (200 ng) or multiple (200 ng/day, 5 days) doses of C- ANP4-23 reduced angiogenesis in the implants relative to the phosphate-buffered saline-treated group. The peptide exerted an inhibitory effect on nitric oxide production (nitrite levels) and had a dual effect on VEGF levels, depending on the number of doses (i.e. stimulation at 4 days after one dose; inhibition at 7 days after five doses). Histological analysis corroborated the biochemical and functional parameters indicative of inhibition of neovascularization (decreased vessel number) by C- ANP4-23. The peptide failed to modulate inflammation in our system. The inhibitory effect of C- ANP4-23 on the angiogenic component of the fibrovascular tissue induced by the synthetic matrix extends the range of the its actions and may indicate its therapeutic potential in controlling angiogenesis in fibroproliferative diseases. [ABSTRACT FROM AUTHOR]

Major histocpmpatibilty complex class I (MHC I) antigen presentation allows CD8+ T cells to detect and eliminate cancerous or virally infected cells. The MHC I pathway is not essential for cell growth and viability and consequently cancers and viruses can evade control by CD8+ T cells by inactivating antigen presentation. In cancers, two common ways for this evasion are the loss of either the MHC I light chain (ß2M) or the cytosol-to-endoplasmic reticulum (ER) peptide transporter (TAP). ß2M-null cells are generally thought to lack the MHC I pathway because the MHC I heavy chain by itself lacks the proper conformation for peptide display. TAP-null cells are thought to have severely defective MHC I antigen presentation because they are incapable of supplying peptides from the cytosol to MHC I molecules in the ER. However, we have found that highly reactive memory CD8+ T cells could still recognize cells that completely lacked ß2M or TAP. This was at least in part because in TAPnull cells, the Sec62 component of the Sec61 translocon supported the transfer of cytosolic peptides into the ER. In ß2M-negative cells, free MHC I heavy chains were able to bind peptides and assume a conformation that was sufficiently recognized by CD8+ T cells. This process required ER chaperones and the peptide-loading complex. We found that these mechanisms supported antigen presentation at a level that was sufficient for memory CD8+ T cells to kill melanoma cells both in vitro and in tumor-bearing mice. The implications for tumor immunotherapy are discussed.