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.

Introduction: Stem cells and cancer cells are known to excrete pro – angiogenic factors such as vascular endothelial growth factor (VEGF). These factors promote angiogenesis of normal as well as cancerous tissues. Objective: The aim of this study is to compare the expressions of growth factors and Human umbilical vein endothelial cells (HUVECs) count in tumoural and non-tumoural angiogenesis model co-cultured with Wharton’s jelly-derived mesenchymal stem cells (WJMSC). Materials & Methods: Different angiogenesis models were prepared as follows; 1) Non-tumoural angiogenesis model, NTAM (indirect co-culture of WJMSCs and HUVECs), 2) Tumoural angiogenesis model, TAM (indirect co-culture of MCF7 and HUVECs) and 3) Stem cells in tumoural angiogenesis model, STAM (indirect co-culture of WJMSCs, MCF7 and HUVECs). Culture of HUVECs alone was prepared as control. The difference in HUVECs count and VEGF concentration were compared between models on day 3 and 6. Results: HUVECs count and VEGF were reduced in STAM compared to TAM with p-value of 0.014 and 0.021, respectively. In contrast, HUVECs count in NTAM was significantly increased compared to control with p-value of 0.018. Conclusion: WJMSCs promote HUVECs proliferation and the up-regulation of pro-angiogenic factors in NTAM. While in STAM, the presence of stem cells with MCF7 seems to inhibit HUVECs proliferation and eventually down regulate the pro-angiogenic factors. Hence, it is suggested that the involvement of WJMSCs in STAM offers an anti-tumour property.

Introduction: Massive chronic intervillositis (MCV) or currently known as chronic intervillositis of unknown aetiology is a rare poorly understood placental lesion. MCV is strongly associated with recurrent spontaneous miscarriages, IUGR and fetal demise. We described a case of MCV in a lady with consecutive recurrent miscarriages. Case report: The patient was a 37-year-old lady who had ten consecutive recurrent first trimester miscarriages within the last 13 years. She has no living child and the relevant blood investigations were not helpful in determining the cause of recurrent miscarriages. Histopathological examination of the conception tissues showed abundant aggregates of CD 68 positive histiocytes primarily within the intervillous spaces associated with increased perivillous fibrin deposition. No significant villitis were seen. The findings were consistent with massive chronic intervillositis. Discussion & conclusion: MCV is associated with high recurrence rate of spontaneous miscarriages. In general, practicing pathologist are unfamiliar with MCV. The histiocytes may be missed during a routine reporting of tissue from products of conception if important clinical informations are not being highlighted to the pathologists. Chronic intervillositis of infectious etiology should be excluded. However the etiology of MCV remains unclear. The histiocytes are maternal in origin which led to the hypothesis of a possible abnormal maternal immune reaction towards the placental tissue in the pathogenesis of MCV. Obstetricians and pathologists should be made aware of this entity. Until today, no proven effective treatment has been proposed to prevent recurrences. Further studies are required in the understanding of this entity and in the prevention of recurrent pregnancy losses.