Project description:To reveal the molecular mechanisms underlying oral ulcerative mucositis-induced pain, we investigated putative pain-associated mediators, pain-related behaviors and gene modulation in a rat oral mucositis model. On day 1 after acetic acid treatment, the mucosal area showed slight redness and swelling but no evidence of ulceration or pain induction. On day 2, oral ulcers were obvious, as was the induction of spontaneous and mechanical pain. In the treated mucosal area, bacterial loading and prostaglandin E2 increased beginning on day 2; no significant changes were observed on day 1. DNA microarray analysis of trigeminal ganglion tissue collected on day 2 identified 32 significantly regulated genes (>1.5-fold change in expression). The up-regulation of the top 3 genes, Hamp (hepcidin antimicrobial peptide), Reg3b (regenerating islet-derived 3β) and Serpina3n (serine peptidase inhibitor A3N), was validated through quantitative RT-PCR. Systemic antibiotic pre-treatment did not increase the mRNA levels. Therefore, we conclude that the oral ulcerative mucositis-induced pain is caused by infectious inflammation of the ulcerative area and stimulates anti-bacterial and anti-peptidase gene expressions in sensory neurons. Oral ulcerative mucositis-induced gene expression in trigeminal ganglion tissue was measured. Ten Wistar rats were divided into the following two groups, control, oral ulcerative mucositis (stomatitis). Five rats were anesthetized with sodium pentobarbital. A piece of filter paper was soaked in 50% acetic acid diluted with water and placed in the labial fornix region of the inferior incisors of rats for 30 sec. Other five rats received only anesthesia without any treatment were used as a control. On day 2 after acetic acid treatment, oral ulcerative mucositis was obvious and trigeminal ganglion tissues in two groups were collected for DNA microarray analysis.
Project description:To reveal the molecular mechanisms underlying oral ulcerative mucositis-induced pain, we investigated putative pain-associated mediators, pain-related behaviors and gene modulation in a rat oral mucositis model. On day 1 after acetic acid treatment, the mucosal area showed slight redness and swelling but no evidence of ulceration or pain induction. On day 2, oral ulcers were obvious, as was the induction of spontaneous and mechanical pain. In the treated mucosal area, bacterial loading and prostaglandin E2 increased beginning on day 2; no significant changes were observed on day 1. DNA microarray analysis of trigeminal ganglion tissue collected on day 2 identified 32 significantly regulated genes (>1.5-fold change in expression). The up-regulation of the top 3 genes, Hamp (hepcidin antimicrobial peptide), Reg3b (regenerating islet-derived 3β) and Serpina3n (serine peptidase inhibitor A3N), was validated through quantitative RT-PCR. Systemic antibiotic pre-treatment did not increase the mRNA levels. Therefore, we conclude that the oral ulcerative mucositis-induced pain is caused by infectious inflammation of the ulcerative area and stimulates anti-bacterial and anti-peptidase gene expressions in sensory neurons.
Project description:Background Toxicity of the oral and gastrointestinal mucosa induced by high-dose melphalan is a clinical challenge with no documented prophylactic interventions or predictive tests. The aim of this study was to describe molecular changes in human oral mucosa and to identify biomarkers correlated with the grade of clinical mucositis. Methods and Findings Ten patients with multiple myeloma (MM) were included. For each patient, we acquired three buccal biopsies, one before, one at 2 days, and one at 20 days after high-dose melphalan administration. We also acquired buccal biopsies from 10 healthy individuals that served as controls. We analyzed the biopsies for global gene expression and performed an immunohistochemical analysis to determine HLA-DRB5 expression. We evaluated associations between clinical mucositis and gene expression profiles. Compared to gene expression levels before and 20 days after therapy, at two days after melphalan treatment, we found gene regulation in the p53 and TNF pathways (MDM2, INPPD5, TIGAR), which favored anti-apoptotic defense, and upregulation of immunoregulatory genes (TREM2, LAMP3) in mucosal dendritic cells. This upregulation was independent of clinical mucositis. HLA-DRB1 and HLA-DRB5 (surface receptors on dendritic cells) were expressed at low levels in all patients with MM, in the subgroup of patients with ulcerative mucositis (UM), and in controls; in contrast, the subgroup with low-grade mucositis (NM) displayed 5–6 fold increases in HLA-DRB1 and HLA-DRB5 expression in the first two biopsies, independent of melphalan treatment. Moreover, different splice variants of HLA-DRB1 were expressed in the UM and NM subgroups. Conclusions Our results revealed that, among patients with MM, immunoregulatory genes and genes involved in defense against apoptosis were affected immediately after melphalan administration, independent of the presence of clinical mucositis. Furthermore, our results suggested that the expression levels of HLA-DRB1 and HLA-DRB5 may serve as potential predictive biomarkers for mucositis severity
Project description:In cancer patients, an elemental diet (ED) reduces adverse effects of chemotherapy, including oral mucositis. However, the detailed mechanism(s) of the healing effects of an ED remains unclear. In this study, the protective effects of the ED, Elental®, were examined against 5-fluorouracil (5-FU)-induced oral mucositis and salivary gland atrophy in mice. Mucositis was induced in female ICR mice by injection of 5-FU. The mice were orally administered Elental® (ED group) or saline (control group). After treatment, whole transcriptome analysis and network analysis were conducted to understand the mechanism(s) of action of Elental® against oral mucositis. Whole transcriptome analysis and Ingenuity Pathways Analysis (IPA) data suggested that Elental® contributed to the recovery of mitochondrial function in 5-FU-damaged salivary glands.
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes
Project description:Few studies have assessed the patterns of parasite populations of rodents over a longitudinal gradient in Chile. In this work, the gastrointestinal helminthic fauna of invasive rodents in Chile was examined to assess the association between their presence/absence and abundance with latitude, host sex, and host body condition, and to assess the coexistence and correlation of the abundance between parasite species. Rodents were obtained from 20 localities between 33 and 43°S. Helminths were extracted from the gastrointestinal tract and identified morphologically. Overall, 13 helminth taxa were obtained. The most frequently identified parasite species was Heterakis spumosa, and the most abundant was Syphacia muris, while Physaloptera sp. was the most widely distributed. No locality presented with a coexistence that was different from that expected by chance, while the abundance of five helminthic species correlated with the abundance of another in at least one locality, most likely due to co-infection rather than interaction. Host sex was associated with parasite presence or abundance, and female sex-biased parasitism was notably observed in all cases. Body condition and latitude presented either a positive or negative association with the presence or abundance of parasites depending on the species. It is notable that the likely native Physaloptera sp. is widely distributed among invasive rodents. Further, gravid females were found, suggesting spillback of this species to the native fauna. The low frequency and abundance of highly zoonotic hymenolepid species suggest that rodents are of low concern regarding gastrointestinal zoonotic helminths.
Project description:Decreased salivary flow rates and/or changes in protein composition reported after autologous hematopoietic stem cell transplantation (ASCT) reduces the protective function of saliva. This might be associated with the development of oral mucositis (OM), an inflammation of the oral mucosa as a result of chemotherapy before ASCT which affects patients, quality of life and risk factor for systemic infections. In this study, a TMT-labelled proteomics experiment, a label-free quantification (LFQ) proteomics experiment and a DIA-MS proteomics experiment were used to identify differences in the salivary proteome between patients with ulcerative OM (uOM; WHO score 2) and those without (nOM).