Effect of Hydrogen Peroxide on Interleukin-8 Synthesis and Death of Caco-2 Cells

Intestinal epithelial cells can secrete interleukin-8 (IL-8), among other substances in response to different stimuli, which plays an important role in mucosal immune response. Above a certain concentration range, hydrogen peroxide causes cell death by necrosis or apoptosis. We investigated the time- and dose-dependent induction of IL-8 by hydrogen peroxide in the human colon adenocarcinoma cell line Caco-2. In addition, the changes of transepithelial electrical resistance and cell death induction in response to hydrogen peroxide were studied. Nonfilter-grown and filter-grown Caco-2 cells were employed in our experiments. Interleukin-8 synthesis was measured by ELISA. Necrosis was determined by DAPI staining of cells, apoptosis by measuring caspase-3 enzyme activity or annexin V staining. In nonfilter-grown Caco-2 cells, 1 mM of hydrogen peroxide induced the highest level of IL-8 production 24 hr after treatment. In filter-grown Caco-2 cells, IL-8 was produced only on the apical side in response to 1 mM of hydrogen peroxide. This level was 10-fold lower than that measured in nonfilter-grown Caco-2 cells 24 hr after the treatment. In filter-grown Caco-2 cells 10 mM hydrogen peroxide induced the highest IL-8 level on the apical as well as basolateral side. Transepithelial electrical resistance decreased markedly upon application of 40 mM hydrogen peroxide. Late effect of hydrogen peroxide was observed in nonfilter-grown Caco-2 cells, as 1 mM hydrogen peroxide caused necrosis after 24 hr while early-necrosis induction occurred in filter-grown cells exposed to 40 mM of hydrogen peroxide after 1 hr. Filter-grown Caco-2 cells were less sensitive to hydrogen peroxide than the nonfilter-grown ones.     

Imatinib accelerates progenitor cell‐mediated liver regeneration in choline‐deficient ethionine‐supplemented diet‐fed mice

Severe chronic hepatic injury can induce complex reparative processes. Ductular reaction and the appearance of small hepatocytes are standard components of this response, which is thought to have both adverse (e.g. fibrosis, carcinogenesis) and beneficial (regeneration) consequences. This complex tissue reaction is regulated by orchestrated cytokine action. We have investigated the influence of the tyrosine kinase inhibitor imatinib on a regenerative process. Ductular reaction was induced in mice by the widely used choline‐deficient ethionine‐supplemented diet (CDE). Test animals were treated daily with imatinib. After 6 weeks of treatment, imatinib successfully reduced the extent of ductular reaction and fibrosis in the CDE model. Furthermore, the number of small hepatocytes increased, and these cells had high proliferative activity, were positive for hepatocyte nuclear factor 4 and expressed high levels of albumin and peroxisome proliferator‐activated receptor alpha. The overall functional zonality of the hepatic parenchyma (cytochrome P450 2E1 and glucose 6 phosphatase activity; endogenous biotin content) was maintained. The expression of platelet‐derived growth factor receptor beta, which is the major target of imatinib, was downregulated. The anti‐fibrotic activity of imatinib has already been reported in several experimental models. Additionally, in the CDE model imatinib was able to enhance regeneration and preserve the functional arrangement of hepatic lobules. These results suggest that imatinib might promote the recovery of the liver following parenchymal injury through the inhibition of platelet‐derived growth factor receptor beta.     

Piezosurgical management of sealer extrusion‐associated mental nerve anaesthesia: A case report

The present report describes a case where sealer extrusion (Sealapex) occurred during root canal obturation of a left lower second premolar tooth, and the patient experienced sudden pain and followed by complete anaesthesia of the lower lip. After 3 weeks of conservative therapy and an unaltered anaesthesia period, piezosurgical removal of the extruded sealer and root‐end resection was performed despite the direct contact with the mental neurovascular bundle. At suture removal, 1 week after surgery, there was no improvement in sensation. Two weeks after the operation, the patient reported some changes, including a short paraesthesia period alternating with anaesthesia. At the fourth post‐operative week, neurosensory function recovered completely. This case represents successful use of the piezoelectric technique for mental nerve decompression and periapical surgery of a lower second premolar with close contact of the mental nerve.     

Three-Dimensionally Printed Individual Drill Sleeve for Depth-Controlled Sections in Third Molar Surgery

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Suppressive mechanisms by Heligmosomoides polygyrus-induced Tregs in C57BL/6 mice change over time and differ to that of naïve mice

Disrupting or harnessing immune suppression is leading to new therapeutic avenues in a number of immune-related diseases. Understanding the suppressive functions of regulatory T cells (Tregs) in different environments is therefore key. Parasitic worms are strong inducers of Tregs and previous research has suggested that parasite-induced Tregs are stronger suppressors than naïve Tregs. In strains susceptible to the intestinal worm Heligmosomoides polygyrus, like C57BL/6 mice, it has been hypothesized that increased Treg suppression downregulates both Th1 and Th2 responses, leading to chronic infections and high worm burden. Here, we show that the suppressive capacity of Tregs is no different between cells from infected and/or naive animals. In vitro suppression induced by CD4⁺CD25⁺Tregs (Peyers’ Patches or the mesenteric lymph nodes), isolated early (day 7, tissue dwelling phase) or late (day 21, luminal phase) during infection was similar to that induced by cells from naïve animals. Suppression was CTLA-4 dependent in Tregs from acute but not chronic infection or in Tregs from naïve animals. This highlights the versatility of Tregs and the importance of extensive Treg characterization prior to potential in vivo manipulation of this cell type.     

The role of the metabolite cargo of extracellular vesicles in tumor progression

Cancer and Metastasis Reviews - Metabolomic reprogramming in tumor and stroma cells is a hallmark of cancer but understanding its effects on the metabolite composition and function of tumor-derived...     

Esthetic perception of changes in facial profile resulting from orthodontic treatment with extraction of premolars: A systematic review

Background

The authors conducted a systematic review to assess changes in patients’ facial profiles resulting from orthodontic treatment with and without extraction of 4 premolars and to identify cephalometric parameters that can assist decision making in borderline cases.

Analyzing Models of Work Addiction: Single Factor and Bi-Factor Models of the Bergen Work Addiction Scale

Work addiction (‘workaholism’) has become an increasingly studied topic in the behavioral addictions literature and had led to the development of a number of instruments to assess it. One such instrument is the Bergen Work Addiction Scale (BWAS - Andreassen et al. 2012 Scandinavian Journal of Psychology, 53, 265-272). However, the BWAS has never been investigated in Eastern-European countries. The goal of the present study was to examine the factor structure, the reliability and cut-off scores of the BWAS in a comprehensive Hungarian sample. This study is a direct extension of the original validation of BWAS by providing results on the basis of representative data and the development of appropriate cut-off scores. The study utilized an online questionnaire with a Hungarian representative sample including 500 respondents (F = 251; M_age = 35.05 years) who completed the BWAS. A series of confirmatory factor analyses were carried out leading to a short, 7-item first-order factor structure and a longer 14-item seven-factor nested structure. Despite the good validity of the longer version, its reliability was not as high as it could have been. One-fifth (20.6 %) of the Hungarians who used the internet at least weekly were categorized as work addicts using the BWAS. It is recommended that researchers use the original seven items from the Norwegian scale in order to facilitate and stimulate cross-national research on addiction to work.     

Rapid CD4+ T‐cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9

Toll‐like receptors (TLRs) can recognize microbial patterns and utilize adaptor molecules, such as‐MyD88 or (TRIF TIR‐domain‐containing adapter‐inducing interferon‐β), to initiate downstream signaling that ultimately affects the initiation of adaptive immunity. In addition to this inflammatory role, TLR5 expression on dendritic cells can favor antigen presentation of flagellin peptides and thus increase the sensitivity of flagellin‐specific T‐cell responses in vitro and in vivo. Here, we examined the role of alternative signaling pathways that might regulate flagellin antigen presentation in addition to MyD88. These studies suggest a requirement for spleen tyrosine kinase, a noncanonical TLR‐signaling adaptor molecule, and its downstream molecule CARD9 in regulating the sensitivity of flagellin‐specific CD4⁺ T‐cell responses in vitro and in vivo. Thus, a previously unappreciated signaling pathway plays an important role in regulating the dominance of flagellin‐specific T‐cell responses.