Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression

Age-related differences in wound healing have been documented but little is known about the wound healing mechanism after burns. Our aim was to compare histological features and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9), collagen IV, K6 and CD44 in the burn wound healing process in aged and young rats.     

Pretransplant Interferon‐γ Secretion by CMV‐Specific CD8+ T Cells Informs the Risk of CMV Replication After Transplantation

In this prospective study we analyzed pretransplant interferon‐γ secretion by cytomegalovirus (CMV)‐specific CD8+ T cells to assess its possible utility in determining the risk of CMV replication after solid organ transplantation. A total of 113 lung and kidney transplant patients were enrolled in the study but only 55 were evaluable. All CMV‐seronegative recipients were pretransplant “nonreactive” (IFNγ <0.2 IU/mL) (11/11), whereas 30/44 (68.2%) CMV‐seropositive (R+) recipients were “reactive” (IFNγ ≥0.2 IU/mL) and 14/44 (31.8%) were “nonreactive”. In the R(+) “nonreactive” group, 7/14 (50%) developed posttransplant CMV replication, whereas the virus replicated only in 4/30 (13.3%) of the R(+) “reactive” patients (p = 0.021). According to the best multivariate model, pretransplant “nonreactive” recipients receiving an organ from a CMV‐seropositive donor had a 10‐fold increased risk of CMV replication compared to pretransplant “reactive” recipients (adjusted OR 10.49, 95% CI 1.88–58.46). This model displayed good discrimination ability (AUC 0.80) and calibration (Hosmer–Lemeshow test, p = 0.92). Negative and positive predictive values were 83.7% and 75%, respectively. The accuracy of the model was 82%. Therefore, assessment of interferon‐γ secretion by cytomegalovirus (CMV)‐specific CD8+ T cells prior to transplantation is useful in informing the risk of posttransplant CMV replication in solid organ transplant patients.     

超高分子聚乙烯颗粒刺激单核细胞高表达CD147/EMMPRIN

目的探讨不同浓度磨损颗粒对单核细胞表达细胞外基质金属蛋白酶诱导剂（CD147/EMMPRIN）的影响。方法根据颗粒/细胞比值实验分为0、1、10、100、500、1000共6组,将不同浓度的超高分子聚乙烯（UHMWPE）颗粒与人单核细胞株THP-1共培养24h,台盼蓝染色检测THP-1细胞存活率,利用流式细胞术、Real-time PCR和Western blot检测THP-1细胞CD147/EMMPRIN的表达。结果加入UHMWPE颗粒前及共培养24h后THP-1细胞存活率均大于90%。流式细胞术、Real-timePCR和Westernblot结果均显示加入UHMWPE颗粒后,CD147/EMMPRIN表达较对照组（即颗粒/细胞比值为0）增加,当颗粒/细胞比值在1-100范围时,CD147/EMMPRIN表达与颗粒浓度正相关,颗粒/细胞比值大于或等于100时,CD147/EMMPRIN稳定保持在高表达水平,不随颗粒浓度升高而变化。结论 UHMWPE颗粒刺激单核细胞高表达CD147/EMMPRIN,并呈浓度依赖性。     

Immunohistochemical analysis of CD45RO+ T cells and vascular endothelial growth factor expression in cyclosporin A-induced rat gingival tissue

Background: The aim of this study is to evaluate CD4⁺, CD8⁺, and CD45RO⁺ T cells, and vascular endothelial growth factor (VEGF) expression in cyclosporin A (CsA)–induced rat overgrown gingival tissue during an 8‐week period. Methods: Sixty male Sprague‐Dawley rats weighing 200 to 250 g were used in this study. Mandibular first molars were ligated with 3–0 silk suture. The rats received daily doses of 0.09% NaCl (control group) or 10 mg/kg body weight of CsA (test group) by intraperitoneal injections. Five rats from the control group and 10 rats from the test group were sacrificed at each experimental period (2, 4, 6, and 8 weeks after the beginning of CsA treatment). The specimens were examined immunohistochemically. Results: CD4⁺, CD8⁺, and CD45RO⁺ T cells, and VEGF expression were more prevalent in the CsA‐treated group than in the control group (P <0.05). VEGF was significantly correlated with CD4⁺ T cells, CD4⁺/CD8⁺ ratio, and CD45RO⁺ cells (P <0.05). Conclusion: Based on our findings, we conclude that VEGF, a major regulator of angiogenesis, and CD4⁺, CD8⁺, and CD45RO⁺ memory T cells play a key role in CsA‐induced gingival overgrowth.     

Increased hippocampal CD38 and systemic inflammation after partial hepatectomy does not induce impairment of spatial cognition

Objective: The role of inflammation in cognitive alterations in a post-operative setting is still not fully understood. Surgical interventions can cause systemic inflammations which eventually can induce neuroinflammation. However, the main causes of functional changes after surgery are still elusive. In this study, we investigated the role of CD38, a TNFα-inducible NADH⁺ cyclase and hydrolase. We assume that CD38 overexpression impairs mitochondrial ATP synthesis. Within the hippocampus, the resulting cellular death could lead to cognitive impairment.

Methods: Seventy-nine Wistar-HAN rats were subjected for three hours either to partial hepatectomy under sevoflurane anaesthesia (‘surgery’), sevoflurane anaesthesia alone (‘anaesthesia’) or control. Rats were randomly selected to determine levels of CD38, TNFα, IL-6, and ATP, for GFAP immunohistochemistry and for Morris Water Maze testing.

Results: Plasma TNFα and IL-6 levels were significantly higher in the surgery group in the immediate post-operative phase. GFAP expression and hippocampal CD38 concentration were significantly elevated 24 h after the intervention in the surgery group as compared to anaesthesia alone and controls. ATP levels did not differ significantly between the three groups. No treatment differences in spatial cognition parameters were found.

Conclusions: Surgery in the form of partial hepatectomy activated the peripheral immune system and induced hippocampal glial activation and a CD38 increase. These changes, however, were not associated with rats’ cognitive impairment ≥24 h after surgery.     

Serum soluble CD163 levels in patients with influenza-associated encephalopathy

Background: Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin–haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. Methods: We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Results: Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Conclusions: Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE.     

Distinct set of kinases induced after retrieval of spatial memory discriminate memory modulation processes in the mouse hippocampus

Protein phosphorylation and dephosphorylation events play a key role in memory formation and various protein kinases and phosphatases have been firmly associated with memory performance. Here, we determined expression changes of protein kinases and phosphatases following retrieval of spatial memory in CD1 mice in a Morris Water Maze task, using antibody microarrays and confirmatory Western blot. Comparing changes following single and consecutive retrieval, we identified stably and differentially expressed kinases, some of which have never been implicated before in memory functions. On the basis of these findings we define a small signaling network associated with spatial memory retrieval. Moreover, we describe differential regulation and correlation of expression levels with behavioral performance of polo‐like kinase 1. Together with its recently observed genetic association to autism‐spectrum disorders our data suggest a role of this kinase in balancing preservation and flexibility of learned behavior. © 2013 Wiley Periodicals, Inc.     

Association among Oral Health,Apical Periodontitis,CD14 Polymorphisms,and Coronary Heart Disease in Middle-aged Adults

Introduction

There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD.

Methods

A case-controlled clinical trial was designed to compare middle-aged adults with acute myocardial infarction or unstable angina (n = 51) within 12 months of the acute event defined as first manifestation with healthy controls (n = 49). Participants were matched for age, sex, and socioeconomic status. Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were analyzed by restriction fragment length polymorphism–polymerase chain reaction.

Results

CHD subjects had a higher prevalence of oral diseases and lower compliance to oral preventive strategies than healthy controls. Multivariate analysis showed a positive association between missing teeth (odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.02–1.85), the number of LEOs (OR = 4.37; 95% CI, 1.69–11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17–29.4), and CHD. No statistically significant association emerged between the CD14 C(−260)T and the CD14 C(−159)T polymorphism, endodontic or periodontal disease, and CHD.

Conclusions

Chronic oral diseases may increase the risk of CHD and may be an unconventional risk factor for CHD.     

Sucralose causes non-selective CD4 and CD8 lymphotoxicity via probable regulation of the MAPK8/APTX/EID1 genes: An in vitro/in silico study

One of the most widely used sweeteners in the world is sucralose. With sweetening power 600 times greater than sucrose, its use grows among those who seek to cut calories. Research shows that when heated, sucralose generates toxic products that attack the organism and interact with DNA. Our objective was to test this sweetener under unheated conditions and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. For this purpose, we made use of lymphocyte cultures and the analysis of their CD3⁺, CD4⁺, and CD8⁺ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. Our results showed that sucralose reduces non-selectively the total lymphocytes due to falls in the levels of the CD4⁺, CD8⁺, and CD4⁺CD8⁺ subpopulations. We observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that sucralose modulates the gene expression, interfering especially with the MAPK8, APTX, and EID1 genes. This article presents the results of an evidence-based approach to the safety of human health in the use of sucralose. Finally, this study points out that sucralose has cytotoxic, genotoxic, and mutagenic effects in the concentrations and conditions tested in human lymphocyte cell culture.