Hyaluronic acid‐dependent protection against UVB‐damaged human corneal cells

Within ultraviolet radiation, ultraviolet B (UVB) is the most energetic and damaging to humans. At the protein level, UVB irradiation downregulates the expression of antioxidant enzymes leading to the accumulation of reactive oxygen species (ROS). Due to lacking of a global analysis of UVB‐modulated corneal proteome, we investigate in vitro the mechanism of UVB‐induced corneal damage to determine whether hyaluronic acid (HA) is able to reduce UVB irradiation‐induced injury in human corneal epithelial cells. Accordingly, human corneal epithelial cell lines (HCE‐2) were irradiated with UVB, followed by incubation with low molecular weight HA (LMW‐HA, 100 kDa) or high molecular weight HA (HMW‐HA, 1,000 kDa) to investigate the physiologic protection of HMW‐HA in UVB‐induced corneal injury, and to perform a global proteomic analysis. The data demonstrated that HA treatment protects corneal epithelial cells in the UVB‐induced wound model, and that the molecular weight of HA is a crucial factor. Only HMW‐HA significantly reduces the UVB‐induced cytotoxic effects in corneal cells and increases cell migration and wound‐healing ability. In addition, proteomic analysis showed that HMW‐HA might modulate cytoskeleton regulation, signal transduction, biosynthesis, redox regulation, and protein folding to stimulate wound healing and to prevent these UVB‐damaged cells from cell death. Further studies evidenced membrane‐associated progesterone receptor component 1 (mPR) and malate dehydrogenase (MDH2) play essential roles in protecting corneal cells from UVB irradiation. This study reports on UVB‐modulated cellular proteins that might play an important role in UVB‐induced corneal cell injury and show HMW‐HA to be a potential substance for protecting corneal cells from UVB‐induced injury. Environ. Mol. Mutagen. 54:429–449, 2013. © 2013 Wiley Periodicals, Inc.     

Analysis of parametric histogram from dynamic contrast‐enhanced MRI: application in evaluating brain tumor response to radiotherapy

Dynamic contrast‐enhanced MRI (DCE MRI) has been used to study tumor response to treatment for many years. In this study, the modified full width at half‐maximum (mFWHM), calculated from the wash‐in slope histogram, is proposed as a parameter for the evaluation of changes in tumor heterogeneity which respond to radiotherapy. Twenty‐five patients with brain tumors were evaluated and divided into the nonresponder group (n = 11) and the responder group (n = 14) according to the Response Evaluation Criteria in Solid Tumors (RECIST). All selected tumors were evaluated by mFWHM ratios of post‐ to pre‐therapy (the ratio was defined as the therapeutic mFWHM ratio, TMR). The changes in kurtosis of the histograms and the averaged K^trans within a tumor were also calculated for comparison. The receiver operating characteristic analysis and Kaplan–Meier curves were used to examine the diagnosis ability. The TMR values were significantly higher in nonresponders than in responders (p < 0.001). When compared with the other two parameters, the proposed method also demonstrated better sensitivity and specificity. When adopting the TMR for the estimation of prognosis after therapy, there was a significant difference between the population survival curves. In conclusion, the derived mFWHM reflects tumor heterogeneity, and the ability to depict patient survival probability from TMR corresponds well with that from RECIST. The results reveal that, in brain tumors, progression may be exhibited not only by tumor size, but also by tumor heterogeneity. Copyright © 2012 John Wiley & Sons, Ltd.     

Cruciferous vegetable consumption and gastric cancer risk: A meta‐analysis of epidemiological studies

The relationship between consumption of cruciferous vegetables (CV) and risk of gastric cancer has been investigated by many studies, but remains controversial. We carried out a meta‐analysis to summarize available evidence from epidemiological studies on this point. Relevant published reports of CV intake and gastric cancer were identified using MEDLINE (PubMed), EMBASE, and Web of Science databases through to the end of September 2012. We pooled the relative risk from individual studies using a fixed‐ or random‐effects model and carried out heterogeneity and publication bias analyses. Sixteen case–control and six prospective studies were included in our analysis. When all studies were pooled, we yielded a significantly inverse association between CV (relative risk = 0.81; 95% confidence interval, 0.75–0.88) intake and gastric cancer risk, with little heterogeneity (Q = 27.27, P = 0.292, I² = 12.0%). Specific analysis for cabbage intake yielded similar result. When separately analyzed, case–control studies of CV intake yielded significant results and the results of prospective studies showed borderline statistical significance. Moreover, significant results were consistent for high‐quality studies, for North American, European, and Asian studies, for studies on males, and for studies on non‐cardia gastric cancer. Findings from this meta‐analysis provide evidence that high intake of CV was inversely associated with the risk of gastric cancer and non‐cardia gastric cancer in humans. Further studies on other specific CV, food preparation methods, and stratified results by anatomic cancer site and histological type should be extended in the future.     

Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross‐sectional study

It has been reported that EMMPRIN is involved in the regulation of immune response and the induction of MMPs production by fibroblasts. The aim of this study was to describe the intestinal gene expression and protein production of EMMPRIN, MMP23 and MMP10 in patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared them with a control group. Gene expression of EMMPRIN, MMP10 and MMP23B was measured by RT‐PCR. In order to determine EMMPRIN and MMP protein expression, colonic tissues were immunostained. The results of the study showed EMMPRIN gene expression was upregulated in rectal mucosa from active (a)UC versus aCD patients (P = .045), remission (r)CD group (P = .0009) and controls (P < .0001). We detected differences between rUC and aCD (P = .004), rCD (P < .0001) or control group (P < .0001). EMMPRIN showed a higher expression in mucosa (intraepithelial lymphocytes), submucosa and adventitia (endothelial cells) from aCD patients. MMP23 levels were increased in aUC and aCD compared to rUC and rCD and the control group (P = .0001). EMMPRIN+/MMP23+─expressing cells were localized mainly in mucosa, muscular and adventitia from active UC patients. MMP10 gene expression was increased in aUC versus CD patients and the control group (P = .0001). MMP10 gene expression is associated with inflammation in UC patients (P = .0001, r² = .585). EMMPRIN+/MMP10+─producing cells were found mainly in all intestinal layers and perivascular inflammatory infiltrates from aUC patients. In conclusion, EMMPRIN, MMP23 and MMP10 were upregulated in patients with active UC versus remission UC , CD and control groups suggesting that, they are involved in the inflammatory process.     

Beyond Helicobacter: dealing with other variants of gastritis—an algorithmic approach

In daily practice, the presence of inflammation in gastric biopsies prompts a mental algorithm, an early question being whether the lesion present is Helicobacter‐associated. If Helicobacter organisms are not found, then there is a further algorithm, governed by the predominant type of inflammatory cells present, and the presence of other features such as intraepithelial lymphocytosis, a subepithelial collagen band, granulomas, coexisting chronic inflammation, focality, and superimposed reactive changes including erosions and ulcers. Each of these generates its own differential diagnosis. If no inflammation is present, then the two major changes specifically looked for are the changes associated with hypergastrinaemia, by far the most common cause of which is treatment with proton pump inhibitors, and reactive changes. These may be present with and without accompanying inflammation, and, when the epithelial changes dominate, the term gastropathy is preferred. In this article, we present an approach to non‐Helicobacter inflammation and gastropathies.