-Acute glucose fluctuations (AGF) often cause high mortality among critically ill patients, but the mechanisms induced by AGF are not clear. Recent studies suggest that endothelial dysfunction is a key factor that leads to high mortality among critically ill patients. Our goal is to evaluate the phenomenon and mechanisms of endothelial dysfunction induced by AGF. In this study, the functions of human umbilical vein endothelial cells (HUVECs) were compared after treatment with sustained high glucose (SHG), AGF in two groups (AGF1 fluctuations between 5 and 16 mM and AGF2 fluctuations between 5 and 25 mM), and normal glucose levels as a control group (CTR). The medium of the groups was changed every 4 h. The influence of AGF on wound healing was also tested on C57BL/6 mice. The results show that cell proliferation, angiogenesis, and migration functions were injured in the SHG and both AGF groups. AGF2 group shows the worse condition in vitro. In vivo, the wound healing was delayed after the AGF treatment. Furthermore, the markers of apoptosis and autophagy were analyzed. We observed that the autophagy changed in all treatment groups, but apoptosis showed no change. To get to know the mechanism of dysfunction and autophagy, we performed the microRNA chip assay and real-time PCR and found miR-1273g-3p remarkably changed in AGF2 group. After the mimic and inhibitor of miR-1273g-3p were transfected during the AGF2 treatment, we found that the dysfunction and autophagy were partially enhanced by miR-1273g-3p mimic and reversed by miR-1273g-3p inhibitor in AGF2 group. Thus, we conclude that AGF can induce more dysfunction and autophagy, and miR-1273g-3p is also an important factor that leads to the injury. glucose fluctuations; endothelial dysfunction; wound healing; autophagy; miR-1273g-3pINCREASING GLYCEMIC VARIABILITY can greatly increase the risk of mortality among critically ill patients. Several previous studies suggest that the variability in glucose levels over time is an important determinant of mortality among critically ill patients (21,22,58). Alternatively, recent evidence shows that glucose fluctuations may influence the development of diabetic complications(4, 47) and may produce more serious injury in organ functions than sustained high blood glucose. Krinsley and Preiser (20) reported that if a blood glucose range of 70 -140 mg/dl is maintained for Ͼ80% of the time, the chances of survival of nondiabetic critically ill adults will be greatly increased. Organ injury induced by glucose toxicity is commonly observed in both intensive care units and endocrine departments. The damage is also observed in in vitro cell culture and animal studies. Therefore, some authors have proposed that "glycemic variability" is a new therapeutic challenge in diabetes and the critical care setting (7).The mechanism of the production of glucose fluctuations is variable in several studies (35)(36)(37)(38)(39)57) in both preclinical and clinical research studies. However, this is not appropriate for the critically ill patient...

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MicroRNA-194 (miR-194), a typical p53 responsive miRNA, serves as a tumor suppressor similar as p53, and has been demonstrated to play an anti-proliferation role in various human cancers. In spite of the pivotal role of p53 during aging process, the knowledge of miR-194's contribution to cellular senescence is limited. We herein sought to explore the role of miR-194 in the replicative senescence and stress-induced senescence of mouse embryonic fibroblasts. Our results unraveled that, compared to young cells, miR-194 is highly expressed in senescent cells, and extra expression of miR-194 significantly triggers the replicative senescence of MEFs and H O -induced senescence of NIH/3T3 cells, while inhibition of miR-194 exhibited the opposite effect. We further unveiled that DNMT3A was a direct and authentic target of miR-194, which has been reported to be closely associated with cellular senescence. Taken together, our data suggest that miR-194 may significantly promote the development of cellular senescence in mouse embryonic fibroblasts, which potentially occurs through inhibiting the DNMT3A expression.

Simvastatin, which is primarily prescribed to lower cholesterol, may also mitigate lung injury caused by sepsis, although the mechanisms remain elusive. This study aimed to evaluate the protective effect of simvastatin on acute lung injury in rats with sepsis and to investigate possible mechanisms. Male Wistar rats were pretreated with simvastatin (0.2 μg/g) for 1 week before cecal ligation and puncture. Treatment with simvastatin demonstrated significant decreases in the concentration of protein, TNF-α, IL-1β, IL-6, and lipocalin 2, and the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid in septic rats. In addition, simvastatin also reduced levels of Evans blue, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and wet/dry lung weight ratios, and increased the activity of superoxide dismutase in lung tissue. Furthermore, expression levels of TLR4, NF-κB p65, and active caspase-3 proteins and Bax mRNA were also decreased by simvastatin. H&E staining showed that severe lung injury occurred in the sepsis group and that lung injury was reduced by treatment with simvastatin. In conclusion, simvastatin improved endothelial permeability and mitigated the inflammatory response of lung tissue, the oxidative stress response, and cell apoptosis by inhibiting the TLR4/NF-κB signaling pathway, thereby alleviating sepsis-induced acute lung injury in rats.

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Background:Non-Hodgkin lymphoma is the fourth most common malignant tumors in children, Burkitt lymphoma (BL) accounts for 30–50% of all pediatric lymphomas. The aim of this study was to investigate the clinicopathologic features, immunophenotype, Epstein-Barr virus (EBV) infection and c-myc gene rearrangement of sporadic BL in children.Methods:Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features, immunohistochemistry, EBV-encoded RNA (EBER) status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.Results:In the 92 cases, male is predominant in sex distribution (M: F = 3.38:1). The average age at diagnosis was 4.97 years. Polypoid BL showed a lower clinical stage (P = 0.002), and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P = 0.024 and 0.053, respectively). The positive expression of CDl0, B-cell lymphoma-6, MUMl and EBER were 95.7% (88 cases), 92.4% (85 cases), 22.8% (21 cases), 41.3% (38 cases), respectively. The expression of MUM1 were not associated with EBV infection status (P = 1.000). c-myc gene rearrangement was detected in 94.6% (87/92). Clinical treatment information for 54 cases was collected, 21 patients died of tumor after surgery alone, 33 patients received surgery and chemotherapy, and of which six patients died shortly afterwords (MUM1 positive expression in 3 cases, P = 0.076).Conclusions:The anatomical location, growth pattern and serum albumin level of BL were associated with biological behavior. MUM1 may be a potential adverse prognostic marker, and not associated with EBV infection status.

Sclerosing angiomatoid nodular transformation can occur in early childhood.

The material in this document is covered by the provisions of the Copyright Act, by Canadian laws, policies, regulations and international agreements. Such provisions serve to identify the information source and, in specific instances, to prohibit reproduction of materials without written permission. For more information visit http://laws.justice.gc.ca/en/showtdm/cs/C-42 AbstractThe objective of this study was to identify household materials that may contribute to the indoor naphthalene concentration in Canadian homes. Ninety-nine household materials including building materials, furnishings, and consumer products were tested.These materials included well-known naphthalene-containing products such as mothballs as well as building and consumer products where naphthalene could have been either added as part of a liquid formulation or used as a chemical intermediate in the manufacture of solid materials and product components. A fast screening method was used to determine the naphthalene concentration in a micro-scale test chamber. The tested materials were ranked based on the naphthalene emission strength combined with the amount of products typically used in homes. As expected, the results showed that mothballs, which had the highest emission factor, are one of the predominant sources.Interestingly, vinyl and wooden furniture with high emission factors and painted walls and ceiling with large surface areas were found to be important sources with the source strength even larger than those of mothballs when maximum emission factors were assumed for these building materials and furnishings. This suggests that some building materials and furnishings could be significant contributors to indoor naphthalene concentrations. This study shows that selecting materials with lower naphthalene emission factors could be one of many ways to reduce the indoor naphthalene concentration.3