Gene and protein expression of epithelial to mesenchymal transition for intestinal and anal fistula: a systematic review

Purpose Intestinal fibrosis is a common complication of inflammatory bowel diseases. However, the possible involvement of epithelial-mesenchymal transition (EMT) has been scarcely investigated. This systematic review aims to search through research papers that are focusing on messenger RNA (mRNA) and protein expression profile in EMT in fistula or in intestinal fibrosis. Methods Electronic exploration was performed until April 24, 2019 through PubMed, Ovid, Science Direct, and Scopus databases with the terms of “fistula” OR “intestinal fibrosis” AND “epithelial-mesenchymal transition”. Two independent reviewers scrutinized the suitability of the title and abstract before examining the full text that met the inclusion criteria. For each study, the sample types that were used, methods for analysis, and genes expressed were identified. The list of genes was further analyzed using DAVID (Database for Annotation, Visualization, and Integrated Discovery) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway. Results There were 896 citations found; however, only 3 studies fulfilled the requirements. Among the EMT-related genes, 5 were upregulated genes at mRNA level while 6 were at protein level. However, only 2 downregulated genes were found at each mRNA and protein level. Of the 4 inflammation-related genes found, 3 genes were upregulated at mRNA level and 1 at protein level. These genes were confirmed to be involved in the development of inflammatory induced fibrosis and fistula through EMT. Results from quantitative real-time polymerase chain reaction analysis were consistent with the process of EMT, confirmed by the western blot protein analysis. Conclusion Many significant genes which are involved in the process of EMT in fistula and intestinal fibrosis have been identified. With high-end technology many more genes could be identified. These genes will be good molecular targets in the development of biomarkers for precision drug targeting in the future treatment of intestinal fibrosis and fistula

Haematological Reference Intervals in a Multiethnic Population

Introduction: Similar to other populations, full blood count reference (FBC) intervals in Malaysia are generally derived from non-Malaysian subjects. However, numerous studies have shown significant differences between and within populations supporting the need for population specific intervals. Methods: Two thousand seven hundred twenty five apparently healthy adults comprising all ages, both genders and three principal races were recruited through voluntary participation. FBC was performed on two analysers, Sysmex XE-5000 and Unicel DxH 800, in addition to blood smears and haemoglobin analysis. Serum ferritin, soluble transferrin receptor and Creactive protein assays were performed in selected subjects. All parameters of qualified subjects were tested for normality followed by determination of reference intervals, measures of central tendency and dispersion along with point estimates for each subgroup. Results: Complete data was available in 2440 subjects of whom 56% (907 women and 469 men) were included in reference interval calculation. Compared to other populations there were significant differences for haemoglobin, red blood cell count, platelet count and haematocrit in Malaysians. There were differences between men and women, and between younger and older men; unlike in other populations, haemoglobin was similar in younger and older women. However ethnicity and smoking had little impact. 70% of anemia in premenopausal women, 24% in postmenopausal women and 20% of males is attributable to iron deficiency. There was excellent correlation between Sysmex XE-5000 and Unicel DxH 800. Conclusion: Our data confirms the importance of population specific haematological parameters and supports the need for local guidelines rather than adoption of generalised reference intervals and cut-offs

Incidence of anaemia, iron deficiency and iron deficiency anaemia.

<p>Incidence of anaemia, iron deficiency and iron deficiency anaemia.</p

Comparison of Reference Intervals of various populations.

<p>Gaza Strip (N = 50,127)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-Sirdah1" target="_blank">[1]</a>.</p><p>Germany(N = 2967)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-Ittermann1" target="_blank">[6]</a>.</p><p>US (N = 7664) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-Beutler1" target="_blank">[4]</a>, (N = not available)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-NHANES1" target="_blank">[5]</a>, (N = not available)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-Hsieh1" target="_blank">[8]</a>.</p><p>UK (N = 700)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-OseiBimpong1" target="_blank">[2]</a>.</p><p>South India(N = 500)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-Subhashree1" target="_blank">[3]</a>.</p><p>Ghana (N = 691)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091968#pone.0091968-Dosoo1" target="_blank">[7]</a>.</p>a<p>19–45 years old.</p>b<p>>45 years old.</p>c<p>20–81 years old.</p>d<p>50–59 years old.</p>e<p>60–69 years old.</p>f<p>19–65 years old.</p>g<p>66 years and above.</p>h<p>16–91 years.</p>i<p>18–70 years.</p>j<p>18–59 years.</p><p>W = White B = Black.</p

Reference intervals from this study compared with previous study.

<p>M =  male, F =  female.</p><p>* Median, range 2.5-97.5 centiles.</p><p>** Ferritin ng/mL<13 excluded.</p>§<p>Reference interval  =  mean±SD.</p