Mucosal Cell Proliferation Research Articles

Appendiceal Mucosal Schwann Cell Proliferation Associated with Incidentally Detected Goblet Cell Adenocarcinoma of Appendix in a Case of Invasive Adenocarcinoma of Sigmoid Colon- A Case Report

Abstract Introduction/Objective Appendiceal mucosal Schwann cell proliferation has been suggested to be a putative histologic marker of appendiceal diverticular disease. Appendiceal Goblet cell adenocarcinoma, (GCA) is amongst the most rare appendiceal tumors with a reported incidence of 0.05 cases per 100,000 population per year in United States. They have features of both neuroendocrine tumors and adenocarcinomas, but behave more similarly to adenocarcinomas. Methods/Case Report Herein, we report a case of appendiceal mucosal schwann cell proliferation associated with incidentally detected Goblet cell adenocarcinoma of appendix in a known case of invasive adenocarcinoma of sigmoid colon. A 75-year-old female presented with sigmoid colon obstruction. Intraoperatively, she was found to have gangrenous and perforated colon, as well as a large obstructing sigmoid mass, and underwent total abdominal colectomy with end-ileostomy. On gross examination, a tan bosselated tumor (up to 3.5 cm) was seen in proximal sigmoid colon. Microscopic examination showed Invasive adenocarcinoma, moderately-differentiated. Appendix was unremarkable on gross examination. Incidentally, the appendix microscopically demonstrated “Goblet cell adenocarcinoma”, histologic grade 1 out of 3 (pathologic stage pTis pN0), present in multiple foci within lamina propria of the distal third of appendix over an area measuring 1.5 cm. Additionally, there were foci of SOX10-positive bland- looking spindle cell proliferation in lamina propria of the appendix. This proliferation is rendered as “Schwann cell proliferation”. Results (if a Case Study enter NA) NA Conclusion One study found that “Schwann cell proliferation” is seen in 42% of appendiceal diverticula cases. It has never been reported in association with “Appendiceal GCA” before. Here we report an intriguing case of Schwann cell proliferation associated with this rare entity of GCA for the first time in literature. Therefore, awareness of such coexistence of these pathologic entities in the same appendix is essential to alert the pathologist to look for GCA, whenever Schwann cell proliferation is encountered in random section of an appendix. This case also emphasizes the importance of being vigilant of the possible presence of other tumors in a specimen with a known tumor.

Research on the signaling pathway and the related mechanism of traditional Chinese medicine intervention in chronic gastritis of the "inflammation-cancer transformation".

Objective: The aim of this study is to uncover the traditional Chinese medicine (TCM) treatments for chronic gastritis and their potential targets and pathways involved in the "inflammation-cancer" conversion in four stages. These findings can provide further support for future research into TCM and its active components. Materials and methods: The literature search encompassed PubMed, Web of Science, Google Scholar, CNKI, WanFang, and VIP, employing keywords such as "chronic gastritis", "gastric cancer", "traditional Chinese medicine", "medicinal herb", "Chinese herb", and "natural plant". Results: Herbal remedies may regulate the signaling pathways linked to the advancement of chronic gastritis. Under the multi-target and multi-pathway independent or combined reaction, the inflammatory microenvironment may be enhanced, leading to repair of damaged gastric mucosal cells, buffering the progress of mucosal atrophic degeneration via the decrease of inflammatory factor expression, inhibition of oxidative stress-induced damage, facilitation of microvascular neovascularization in the gastric mucosa and regulation of the processes of gastric mucosal cell differentiation and proliferation. Simultaneously, the decreased expression of inflammatory factors may impact the expression of associated oncogenes and regulate the malignant proliferation of cells, thereby achieving the treatment and prevention objectives of gastric cancer through the reduction of cell metastasis and apoptosis. Conclusion: Chinese medicine formulations and individual drugs can be utilised at various stages of the "inflammation-cancer" progression of chronic gastritis to prevent and treat gastric cancer in a multi-level, multi-targeted, and multi-directional fashion. This can provide guidance for the accurate application of medicines during different stages of "inflammation-cancer" transformation. New insights into the mechanism of inflammation-cancer transformation and the development of novel drugs for chronic gastritis can be gained through an extensive investigation of TCM treatment in this condition.

Knocking Down HN1 Blocks Helicobacter pylori-Induced Malignant Phenotypes in Gastric Mucosal Cells and Inhibits Gastric Cancer Cell Proliferation, Cytoskeleton Remodeling, and Migration.

Helicobacter pylori (H. pylori) is implicated in the aberrant proliferation and malignant transformation of gastric mucosal cells, heightening the risk of gastric cancer (GC). HN1 is involved in the development of various tumors. However, precise mechanistic underpinnings of HN1 promoting GC progression in H. pylori remain elusive. The study collected 79 tissue samples of GC patients, including 47 with H. pylori-positive GC and 32 H. pylori-negative controls. Using human gastric epithelial cells (GES-1) and human gastric adenocarcinoma cells (HGC-27), the effect of overexpression / knocking down of HN1 and H. pylori infection was evaluated on cell function (proliferation, migration, apoptosis), cytoskeleton, and expression of cell malignant phenotype factors that promote the malignant biological behavior of cancer cells. The expression of HN1 in GC tissues is higher than that in paracancerous tissue and is closely related to infiltration, lymphatic metastasis, distant metastasis, survival, and H. pylori infection. Downregulation of HN1 effectively hinders the ability of H. pylori strains 26695 and SS1 to promote migration of GES-1 and HGC-27 cells, while lowering the expression of key indicators associated with malignant phenotype. Downregulated GSK3B, β-catenin, and Vimentin after knockdown Integrinβ1, but HN1 expression remained largely unchanged, when HN1 and Integrinβ1 were knocked down, GSK3B, β-catenin, and Vimentin expression were considerably reduced. Our research demonstrated the crucial role of HN1 in H. pylori-induced acquisition of a malignant phenotype in GES-1 cells. Knockdown of HN1 blocked the pathogenic mechanism of H. pylori-induced GC and downregulated the expression of GSK3Β, β-catenin and Vimentin via Integrin β1.

Review of yeast culture concerning the interactions between gut microbiota and young ruminant animals.

Microorganisms inhabit the gastrointestinal tract of ruminants and regulate body metabolism by maintaining intestinal health. The state of gastrointestinal health is influenced not only by the macro-level factors of optimal development and the physiological structure integrity but also by the delicate equilibrium between the intestinal flora and immune status at the micro-level. Abrupt weaning in young ruminants causes incomplete development of the intestinal tract resulting in an unstable and unformed microbiota. Abrupt weaning also induced damages to the microecological homeostasis of the intestinal tract, resulting in the intestinal infections and diseases, such as diarrhea. Recently, nutritional and functional yeast culture has been researched to tackle these problems. Herein, we summarized current known interactions between intestinal microorganisms and the body of young ruminants, then we discussed the regulatory effects of using yeast culture as a feed supplement. Yeast culture is a microecological preparation that contains yeast, enriched with yeast metabolites and other nutrient-active components, including β-glucan, mannan, digestive enzymes, amino acids, minerals, vitamins, and some other unknown growth factors. It stimulates the proliferation of intestinal mucosal epithelial cells and the reproduction of intestinal microorganisms by providing special nutrient substrates to support the intestinal function. Additionally, the β-glucan and mannan effectively stimulate intestinal mucosal immunity, promote immune response, activate macrophages, and increase acid phosphatase levels, thereby improving the body's resistance to several disease. The incorporation of yeast culture into young ruminants' diet significantly alleviated the damage caused by weaning stress to the gastrointestinal tract which also acts an effective strategy to promote the balance of intestinal flora, development of intestinal tissue, and establishment of mucosal immune system. Our review provides a theoretical basis for the application of yeast culture in the diet of young ruminants.

Reduced Proliferative Capacity and Defense against Staphylococcus aureus in Human Nasal Mucosal Epithelium Lacking ZNF365

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nose characterized by barrier disruption and environmental susceptibility, and the deletion of ZNF365 may be a factor inducing these manifestations. However, there is no study on the mechanism of action between CRSwNP and ZNF365. Therefore, this study focuses on the effect of the zinc finger protein ZNF365 on the proliferation of nasal mucosal epithelial cells and their defense against Staphylococcus aureus (S. aureus). Methods: Immunohistochemistry and Western blot were applied to verify the changes of ZNF365 expression in nasal polyp tissues and control tissues, as well as in primary epithelial cells. ZNF365 was knocked down in human nasal mucosa epithelial cell line (HNEpc), and the proliferation, migration, and transdifferentiation of epithelium were observed by immunofluorescence, QPCR, CCK8, and cell scratch assay. The changes of mesenchymal markers and TLR4-MAPK-NF-κB pathway were also observed after the addition of S. aureus. Results: ZNF365 expression was reduced in NP tissues and primary nasal mucosal epithelial cells compared to controls. Knockdown of ZNF365 in HNEpc resulted in decreased proliferation and migration ability of epithelial cells and abnormal epithelial differentiation (decreased expression of tight junction proteins). S. aureus stimulation further inhibited epithelial cell proliferation and migration, while elevated markers of epithelial-mesenchymal transition and inflammatory responses occurred. Conclusion: ZNF365 is instrumental in maintaining the proliferative capacity of nasal mucosal epithelial cells and defending against the invasion of S. aureus. The findings suggest that ZNF365 may participate in the development of CRSwNP.

UBE2W overexpression promotes proliferation of intestinal mucosal cells in mice with chemically induced colitis

To explore the effect of UBE2W overexpression on proliferation of intestinal mucosal cells in a mouse model of dextran sulfate sodium (DSS)-induced colitis. In a mouse model of colitis induced by exposure to DSS in drinking water, UBE2W expression in the colon tissue was detected by RT-PCR and Western blotting. Ten mouse models of colitis were randomized for injection of adenovirus AAV2/9 myc-UBE2W or control AAV2/9 via the tail vein (n=5), and the changes in body weight were recorded and the histological score of the colon were graded using HE staining. Ki67 and BrdU expressions in the colon mucosal cells were detected with immunohistochemistry. The effect of UBE2W overexpression on proliferation of 293T and HCT116 cells was observed using CCK-8 kit. Compared with normal mice, the mouse models with DSS-induced colitis showed significantly lowered expressions of UBE2W mRNA and protein in the colon tissues. The mouse models with AAV2/9 myc-UBE2W injection had a lower body weight loss than those with control AAV2/9 injection, and the difference was the most distinct on days 9 and 10 (P < 0.05). AAV2/9 myc-UBE2W injection significantly decreased the histological score (P < 0.05) and increased Ki67 and BrdU expressions in the colon mucosal cells in the mouse models (P < 0.05). In both 293T and HCT116 cells, UBE2W overexpression significantly promoted cell proliferation at 72 h and 96 h after plasmid transfection (P < 0.05). UBE2W overexpression provide protection of the colon mucosal cells and promotes recovery of colitis in mice possibly by promoting proliferation of the colon mucosal cells.

Combinations of EGFR and MET inhibitors reduce proliferation and invasiveness of mucosal melanoma cells.

Mucosal melanoma (MM) is a very rare and aggressive type of cancer for which immunotherapy or targeted therapy such as BRAF/MEK inhibitors, used in cutaneous melanoma, usually fail. Due to our earlier experience showing the high effectiveness of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) inhibitors in reducing the activation of the MAPK and PI3K/AKT signalling pathways, we aim to test whether these drugs would also be effective for mucosal melanoma. Cells representing two commercially available mucosal melanoma cell lines (GAK and HMVII) and one cell line obtained from a patient's vaginal melanoma were treated with MET or EGFR inhibitors, or combinations of these agents. The dual-inhibitor treatment strategy resulted in a decrease of cell proliferation, migration and invasion. Moreover, combinations of inhibitors led to reduction of pEGFR/EGFR and pMET/MET ratio and downregulation of PI3K/AKT and MEK/ERK1/2-based signalling pathways. Our findings indicate a potential therapeutic strategy based on EGFR and MET inhibitors in mucosal melanoma, which should be further evaluated in vivo and in clinical experiments. They also suggest that targeting multiple receptor tyrosine kinases may block signalling crosstalk and possibly delay the appearance of resistance to kinase inhibitors in mucosal melanoma cells.

Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During exvivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

Maternal high-fat diet increases the susceptibility of offspring to colorectal cancer via the activation of intestinal inflammation.

A high-fat diet plays a key role in the pathogenesis of colorectal cancer, and this effect on the gut can also occur in the offspring of mothers with a high-fat diet. In this review, we discuss the role of a high-fat diet in the pathogenesis of colorectal cancer and summarize the effects of a maternal high-fat diet on the activation of inflammation and development of colorectal cancer in offspring. Studies have found that a maternal high-fat diet primarily induces an inflammatory response in the colorectal tissue of both the mother herself and the offspring during pregnancy. This leads to the accumulation of inflammatory cells in the colorectal tissue and the release of inflammatory cytokines, which further activate the NF-κb and related inflammatory signaling pathways. Research suggests that high levels of lipids and inflammatory factors from mothers with a high-fat diet are passed to the offspring through the transplacental route, which induces colorectal inflammation, impairs the intestinal microecological structure and the intestinal barrier, and interferes with intestinal development in the offspring. This in turn activates the NF-κb and related signaling pathways, which further aggravates intestinal inflammation. This process of continuous inflammatory stimulation and repair may promote the uncontrolled proliferation of colorectal mucosal cells in the offspring, thus increasing their susceptibility to colorectal cancer.

Ascidian-Inspired Temperature-Switchable Hydrogels with Antioxidant Fullerenols for Protecting Radiation-Induced Oral Mucositis and Maintaining the Homeostasis of Oral Microbiota.

A key characteristic of radiation-induced oral mucositis (RIOM) is oxidative stress mediated by the "reactive oxygen species (ROS) storm" generated from water radiolysis, resulting in severe pathological lesions, accompanied by a disturbance of oral microbiota. Therefore, a sprayable in situ hydrogel loaded with "free radical sponge" fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5-trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature-switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)-modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH-loaded MGA hydrogels whether pre-irradiation prophylactic administration or post-irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation-induced excess ROS and up-regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof-of-principle evidence for the oral radioprotection of FOH by blocking the "ROS storm", but also provides an effective and easy-to-use hydrogel system for mucosal in situ administration.

FTO-mediated m6A modification promotes malignant transformation of gastric mucosal epithelial cells in chronic Cag A+ Helicobacter pylori infection.

Cag A+ Helicobacter pylori chronic infection cause malignant transformation of the human gastric mucosa. N6-methyladenosine (m6A) modifications are the most common and abundant mRNA modifications and one of the pathways affecting tumorigenicity and tumor progression. However, the role of m6A modification in the process of chronic H. pylori infection leading to malignant transformation of gastric mucosa is unclear. In this study, we used Cag A- and Cag A+H. pylori chronic infection to establish cellular models in GES-1 cells and analyzed the cellular morphology, proliferation, apoptosis, invasiveness and tumorigenicity of gastric mucosal epithelial cells. The m6A expression levels of GES-1 cells after chronic infection with Cag A- and Cag A+H. pylori were examined, and modifying effect of FTO (the fat mass and obesity-associated protein) on CD44 was verified by MeRIP-qPCR. Finally, the FTO expression changes and m6A expression levels were further validated in clinical gastric cancer tissues. Chronic Cag A+H. pylori-infected GES-1 cells exhibit altered cell morphology, apoptosis inhibition, abnormal proliferation, enhanced migration, colony formation, and increased stem cell-like properties. Meanwhile, FTO and CD44 expression was enhanced, and FTO may induce malignant transformation of gastric mucosa by regulating CD44 mRNA m6A methylation modifications. We verified the effect of chronic stimulation of Cag A+H. pylori on malignant transformation of gastric mucosal epithelium. revealing the possibility of FTO in promoting malignant transformation of gastric mucosa by modifying CD44 mRNA methylation, suggesting that FTO expression is a potential molecule for malignant transformation of gastric mucosal epithelial cells.

Brucea javanica oil alleviates intestinal mucosal injury induced by chemotherapeutic agent 5-fluorouracil in mice.

Background: Brucea javanica (L.) Merr, has a long history to be an anti-dysentery medicine for thousand of years, which is commonly called "Ya-Dan-Zi" in Chinese. The common liquid preparation of its seed, B. javanica oil (BJO) exerts anti-inflammatory action in gastrointestinal diseases and is popularly used as an antitumor adjuvant in Asia. However, there is no report that BJO has the potential to treat 5-Fluorouracil (5-FU)-induced chemotherapeutic intestinal mucosal injury (CIM). Aim of the study: To test the hypothesis that BJO has potential intestinal protection on intestinal mucosal injury caused by 5-FU in mice and to explore the mechanisms. Materials and methods: Kunming mice (half male and female), were randomly divided into six groups: normal group, 5-FU group (5-FU, 60mg/kg), LO group (loperamide, 4.0mg/kg), BJO group (0.125, 0.25, 0.50g/kg). CIM was induced by intraperitoneal injection of 5-FU at a dose of 60mg/kg/day for 5 days (from day 1 to day 5). BJO and LO were given orally 30min prior to 5-FU administration for 7days (from day 1 to day 7). The ameliorative effects of BJO were assessed by body weight, diarrhea assessment, and H&E staining of the intestine. Furthermore, the changes in oxidative stress level, inflammatory level, intestinal epithelial cell apoptosis, and proliferation, as well as the amount of intestinal tight junction proteins were evaluated. Finally, the involvements of the Nrf2/HO-1 pathway were tested by western blot. Results: BJO effectively alleviated 5-FU-induced CIM, as represented by the improvement of body weight, diarrhea syndrome, and histopathological changes in the ileum. BJO not only attenuated oxidative stress by upregulating SOD and downregulating MDA in the serum, but also reduced the intestinal level of COX-2 and inflammatory cytokines, and repressed CXCL1/2 and NLRP3 inflammasome activation. Moreover, BJO ameliorated 5-FU-induced epithelial apoptosis as evidenced by the downregulation of Bax and caspase-3 and the upregulation of Bcl-2, but enhanced mucosal epithelial cell proliferation as implied by the increase of crypt-localized proliferating cell nuclear antigen (PCNA) level. Furthermore, BJO contributed to the mucosal barrier by raising the level of tight junction proteins (ZO-1, occludin, and claudin-1). Mechanistically, these anti-intestinal mucositis pharmacological effects of BJO were relevant for the activation of Nrf2/HO-1 in the intestinal tissues. Conclusion: The present study provides new insights into the protective effects of BJO against CIM and suggests that BJO deserves to be applied as a potential therapeutic agent for the prevention of CIM.

Acute toxicity of essential oils of Aloysia triphylla (L'Hér.) Britton, Lippia gracilis Schauer, and Piper aduncum L. in Colossoma macropomum (Cuvier, 1818).

The aim of this study was to determine the acute toxicity of the essential oils (EOs) of Aloysia triphylla, Lippia gracilis and Piper aduncum in juvenile tambaqui (Colossoma macropomum), and evaluate the possible histopathological alterations in their gills. For the acute toxicity tests, juvenile tambaqui (n=24/treatment) were distributed in six treatments with three replicates, which comprised the control and five EO concentrations of A. triphylla (60, 80, 100, 120 and 140 mg L-1), L. gracilis (35, 40, 45, 50 and 55 mg L-1) and P. aduncum (42.5, 45, 47.5, 50 and 52.5 mg L-1), with an exposure period of 4 h. The mortality rate and severity of damage to the tambaqui gills were proportional to the increase in the concentration of the EO, with LC50-4 h values estimated at 109.57 mg L -1 for A. triphylla, 41.63 mg L -1 for L. gracilis and 48.17 mg L -1 for P. aduncum. The main morphological damages observed in the gills of the tambaqui exposed to the three EOs, were Grade I: hypertrophy and hyperplasia of lamellar epithelial cells, lamellar fusion, epithelial detachment, capillary dilation and constriction, proliferation of chloride cells and mucosal cells and edema; in low frequency Grade II damage as epithelial rupture and lamellar aneurysm. Necrosis (Grade III damage) was observed only in gill lamellae exposed to P. aduncum EO (47.5, 50.0 and 52.5 mg L-1). Concentrations of EOs below LC50-4 h can be used sparingly, for short periods of exposure for the treatment of diseases in tambaqui breeding.

Clinical and Histopathological Characteristics of Colorectal Cancer in Iraq between 2015-2021.

Colorectal cancer (C.R.C.) is the commonest malignancy in the gastrointestinal tract and is the fourth leading reason behind cancer-associated death in the world. It usually begins with the non-cancerous proliferation of mucosal epithelial cells. These growths are polyps and might grow gradually for 10-20 years before becoming cancerous. This study was designed to investigate the epidemiology of the diagnosed cases of colorectal cancer from 2015 to 2021 in Baghdad. A total of 60 cases of different colorectal cancer samples were collected from Medical City Teaching Hospital, Baghdad, and private labs. Clinical information was also collected, including patients' age, tumor size, gender and location, pathological grade, and stage. Results revealed a high incidence of C.R.C. in patients aged 60-90 years for the rate of 40.3%, with a high frequency in the left colon of 59.6%. The dominant tumor size was 5cm in malignant cases, and a high incidence of C.R.C. was seen in the female by 52.0%. While the most frequent tumor stage was stage I.I.A., with a rate of 59.6%, and moderately differentiated was the foremost one with 67.3% (P≤0.05). The most common type of C.R.C. in Iraq is adenocarcinoma, which occurs in patients older than 60years and presented at the I.I.A. stage of disease with moderate tumor grade. Early disease detection and diagnosis are effective in its control and treatment.

Evaluation and validation of chemotherapy-specific diarrhoea and histopathology in rats.

Chemotherapy-induced mucositis is characterized by diarrhoea and villous atrophy. However, it is not well-understood why diarrhoea arises, why it only occurs with some chemotherapeutics and how it is related to villus atrophy. The objectives in this study were to determine (i) the relationship between chemotherapy-induced diarrhoea and villus atrophy and to (ii) establish and validate a rat diarrhoea model with clinically relevant endpoints. Male Wistar Han IGS rats were treated with saline, doxorubicin, idarubicin, methotrexate, 5-fluorouracil, irinotecan or 5-fluorouracil+irinotecan. After 72 h, jejunal tissue was taken for morphological, apoptotic and proliferative analyses, and faecal water content and change in body weight were determined. All treatments except methotrexate caused a similar reduction (≈42%) in villus height, but none of them altered mucosal crypt cell proliferation or apoptosis. Doxorubicin, idarubicin, irinotecan and 5-fluorouracil+irinotecan caused body weight reduction, but only irinotecan and idarubicin caused diarrhoea. No direct correlation between diarrhoea and villus height or body weight loss was observed. Therefore, studies of the mechanisms for chemotherapy-induced diarrhoea should focus on functional factors. Finally, the irinotecan and idarubicin diarrhoea models established in this study will be useful in developing supportive treatments of this common and serious adverse effect in patients undergoing chemotherapy.

Therapeutic approaches to colorectal cancer via strategies based on modulation of gut microbiota.

Colorectal cancer (CRC) ranks third in terms of global incidence and second in terms of death toll among malignant tumors. Gut microbiota are involved in the formation, development, and responses to different treatments of CRC. Under normal physiological conditions, intestinal microorganisms protect the intestinal mucosa, resist pathogen invasion, and regulate the proliferation of intestinal mucosal cells via a barrier effect and inhibition of DNA damage. The composition of gut microbiota and the influences of diet, drugs, and gender on the composition of the intestinal flora are important factors in the early detection of CRC and prediction of the results of CRC treatment. Regulation of gut microbiota is one of the most promising new strategies for CRC treatment, and it is essential to clarify the effect of gut microbiota on CRC and its possible mechanisms to facilitate the prevention and treatment of CRC. This review discusses the role of gut microbiota in the pathogenesis of CRC, the potential of gut microbiota as biomarkers for CRC, and therapeutic approaches to CRC based on the regulation of gut microbiota. It might provide new ideas for the use of gut microbiota in the prevention and treatment of CRC in the near future and thus reduce the incidence of CRC.

Interferon Regulatory Factor 4 (IRF4) Promotes Lipopolysaccharide-Induced Colonic Mucosal Epithelial Cell Proliferation by Regulating Macrophage Polarization

Introduction: Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of colon and rectum. Interferon regulatory factor 4 (IRF4) mediates macrophage anti-inflammatory phenotype (alternatively activated macrophages [M2]). This study aimed to investigate the mechanism of IRF4 in lipopolysaccharide (LPS)-induced colonic mucosal epithelial cell proliferation via the regulation of macrophage polarization. Methods: Human bone marrow-derived macrophages were subjected to interleukin 4 (IL-4) induction. M2 macrophages were identified using flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). IRF4 expression in M2 macrophages was detected using Western blot and qRT-PCR. IRF4 expression was silenced in M2 macrophages. IL-10 mRNA expression and protein level were detected using qRT-PCR and Western blot. The binding relation between IRF4 and IL-10 was verified using dual-luciferase and chromatin immunoprecipitation assays. Macrophages under different treatments were cocultured with LPS-induced human colonic mucosal epithelial cells. The levels of inflammatory factors (TNF-α, IL-6, and IL-1β) were detected using enzyme-linked immunosorbent assay. The proliferation of inflammatory cells was measured using Cell Counting Kit-8 assay, and the healing of inflammatory cells was detected using wound healing assay. Results: M2 macrophages alleviated LPS-induced inflammatory responses. IRF4 bound to IL-10 and promoted IL-10 expression. Inhibition of IRF4 reduced IL-10 expression and attenuated the alleviating effect of M2 macrophages on inflammatory responses. Inhibition of IRF4 combined with IL-10 overexpression enhanced the promoting effect of M2 macrophages on inflammatory healing. Conclusion: IRF4 promoted colonic mucosal epithelial cell proliferation by increasing IL-10 expression and regulating macrophage polarization to M2 phenotype, which might be related to UC mucosal healing.

Purple Sweet Potato Reduces Malondialdehyde and TNF-a, Increases p53, and Protects Histopathological Appearance in Formaldehyde-induced Nasopharyngeal Carcinoma Rats

BACKGROUND:Purple sweet potato tuber ethanol extract (PSPTEE) has been known to have benefits in various disease, including to prevent nasopharyngeal carcinoma (NPC). However, there has been no research on PSPTEE in preventing the proliferation of nasopharyngeal mucosal epithelial cells induced by formaldehyde through the oxidative stress mechanisms and inflammatory process. Studies have proven the effect of PSP on various cancer cells, but the carcinogenesis process of the nasopharyngeal mucosal epithelium is still limited. Hence, this study aimed to demonstrate the mechanism for preventing histopathology changes with PSPTEE due to formaldehyde exposure.METHODS: Thirty-two formaldehyde-induced Wistar rats were treated with or without 1g/kgBW/day PSPTEE for 16 weeks. Malondialdehyde (MDA) level were examined with spectrophotometry method, while tumor necrosis factor (TNF)-α and p53 with enzyme linked immunosorbent assay (ELISA) method. The histopathology appearance of the nasopharyngeal epithelium was observed with hematoxylin-eosin (HE) staining.RESULTS: MDA and TNF-α levels in control and treatment group were 22.89±2.84 μM; 9.83±0.89 μM and 84.18±11.58 ng/L; 73.92±10.59 ng/L, respectively, and they showed significant difference. Meanwhile, the level of p53 showed no significant difference. Histopathology appearance showed a significant difference. Path analysis for MDA, TNF-α and p53 levels contributed 28.7% to histopathology appearance. MDA have an effect on significant direct effect on TNF-α. TNF-α has a significant direct effect to histopathological appearance. Indirect influence MDA on histopatological appearance were smaller than the direct effect. TNF-α has the greatest influence on histopatological appearance.CONCLUSION: Formaldehyde induces the histopathology appearance in nasopharyngeal epithelium. This study also demonstrates the mechanism to prevent the nasopharynx epithelial histopathology appearance by administration of PSPTEE.KEYWORDS: PSP, MDA, TNF-α, p53, nasopharynx epithelial

Folic acid protects and heals gastric mucosa: role of acid output, inflammatory cytokines, angiogenic and growth factors

BackgroundFolic acid modulates gastrointestinal inflammatory disorders via a number of suggested gastroprotective mechanisms. Gastric acid, inflammation, cell proliferation and angiogenesis play significant role in gastroprotection and restoration of gastrointestinal mucosal integrity following injury. This two-section-study assessed (1) acid output, parietal cell mass, neutrophil infiltration and inflammation after 6 h pyloric ligation, and (2) healing via inflammation, mucosa cell proliferation and angiogenesis in acetic acid induced gastric ulcer in albino Wistar rats upon pre-treatment with Folic acid (FA).ResultsFolic acid significantly lessens the mucosa injury associated with pylorus ligation in a dose-dependent manner. Acid output, parietal cell mass and neutrophil infiltration reduced significantly when compared with the control group. In the acetic acid ulcer group, FA equally reduced ulcer severity (p < 0.05). Moreover, EGFR and Ki-67 were enhanced, while CD31 and Factor VIII were significantly enhanced only on day 10. Also, EGF and VEGF were enhanced, but TNF-α and IL-1β were suppressed in favour of IL-4 and IL-10 dose-dependently in both studies.ConclusionThese results suggest that folic acid supplementation protects the stomach mucosa with reduced gastric acid and inflammation, and also accelerates the healing of ulcers via enhanced mucosal cell proliferation and angiogenesis.

Phytochemical Analysis, Antioxidant, and Wound Healing Activity of Pluchea indica L. (Less) Branch Extract Nanoparticles.

Proliferation and migration of keratinocytes and fibroblasts play an important role in cutaneous wound healing, while oral mucosal squamous cell proliferation and migration are crucial for oral wound healing. In this study, the phytochemical profile of Pluchea indica branch ethanolic extract was characterized. The bioactive compound of Pluchea indica branch ethanolic extract was identified and analyzed by the validated HPLC method. The nanoparticles of P. indica branch extract were formulated by solvent displacement method to increase the solubility and the colloidal stability of the extract. The stability of the nanoparticles was investigated by using the dynamic light scattering technique. Effects of P. indica crude extract and nanoparticles on cell viability, proliferation and migration of primary epidermal keratinocytes, human dermal fibroblasts, and oral mucosal keratinocyte cells were investigated by MTT assay and scratch assay, respectively. The results showed that P. indica branch extract contained a high content of total phenolic and total flavonoids. The HPLC analysis revealed that the main compound in the extract was 4,5-O-dicaffeoylquinic acid. The cell viability of the extract and nanoparticles decreased when cells were exposed to a high concentration of extract and nanoparticles. These results demonstrate that P. indica branch extract and extract nanoparticles at specific concentrations possess in vitro wound healing activity and they may be possibly used to treat different types of wounds including dermal and oral mucosal wounds.