5-Fluorouracil (5-FU) is a commonly used drug for the treatment of malignant cancers. However, approximately 80% of patients undergoing 5-FU treatment suffer from gastrointestinal mucositis. The aim of this report was to identify the drug target for the 5-FU-induced intestinal mucositis. 5-FU-induced intestinal mucositis was established by intraperitoneally administering mice with 100 mg/kg 5-FU. Network analysis of gene expression profile and bioluminescent imaging were applied to identify the critical molecule associated with 5-FU-induced mucositis. Our data showed that 5-FU induced inflammation in the small intestine, characterized by the increased intestinal wall thickness and crypt length, the decreased villus height, and the increased myeloperoxidase activity in tissues and proinflammatory cytokine production in sera. Network analysis of 5-FU-affected genes by transcriptomic tool showed that the expression of genes was regulated by nuclear factor-κB (NF-κB), and NF-κB was the central molecule in the 5-FU-regulated biological network. NF-κB activity was activated by 5-FU in the intestine, which was judged by in vivo bioluminescence imaging and immunohistochemical staining. However, 5-aminosalicylic acid (5-ASA) inhibited 5-FU-induced NF-κB activation and proinflammatory cytokine production. Moreover, 5-FU-induced histological changes were improved by 5-ASA. In conclusion, our findings suggested that NF-κB was the critical molecule associated with the pathogenesis of 5-FU-induced mucositis, and inhibition of NF-κB activity ameliorated the mucosal damage caused by 5-FU.

Both periodontitis and osteoporosis have similar sign of bone resorption in nature. However, the relationship of the severity between these 2 bone-loss diseases is still uncertain.The aim of this study was to investigate the association between the severity of osteoporosis and periodontitis regarding the impact of oral hygiene maintenance. In total, 35,127 osteoporosis patients and 50,498 comparisons were derived from the Longitudinal Health Insurance Database of Taiwan between 2000 and 2010. The population was subdivided into groups according to the different level oral hygiene maintenance and the severity of periodontitis and osteoporosis. The association between osteoporosis and periodontitis was estimated by multinomial logistic regression and rank correlation by Kendall rank correlation test, presented by odds ratio (OR), and 5% confidence intervals (CIs).After controlling the age, sex, and comorbidities, variables in the good oral hygiene maintenance population, we found that periodontitis raised 1.29-fold risk of osteoporosis (95% CI = 1.12-1.49); the risk of osteoporosis was increased with the elevated severity of periodontitis from 1.27 (95% CI = 1.08-1.48) to 1.38 (95% CI = 1.01-1.89). There is a positive correlation between the severity of periodontitis and osteoporosis occurrence in this population (OR = 1.27-1.46; Kendall rank correlation test P = 0.0003). In the poor oral hygiene maintenance population, periodontitis patients had 6.02-fold risk of osteoporosis than those who without periodontitis (95% CI = 4.65-7.81); the risk of osteoporosis was increased with periodontitis severity from 5.96 (95% CI = 4.48-7.92) to 6.37 (95% CI = 3.36-12.1).This result indicated the periodontitis and osteoporosis are conjunctive. The sudden periodontal breakdown of those who with good oral hygiene maintenance might be an indicator for the risk of osteoporosis; if those who were diagnosed as osteoporosis must pay more attention to their periodontal health. Good oral hygiene maintenance might be a crucial factor for preventing the deterioration of osteoporosis progressing; the oral hygiene maintenance plays a significant influence on the association between periodontitis and osteoporosis.

Little is currently known about the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study sought to determine the incidence of BRONJ in osteoporotic patients. We also sought to identify the nature and types of risk factors of osteonecrosis of jaw (ONJ) related to the use of oral bisphosphonates (BPs). Data from the National Health Insurance system of Taiwan. This cohort study included 19,399 adult osteoporosis patients received dental extraction in 2000-2010 (osteoporosis cohort) and 38,669 age and gender matched comparisons selected from dental extraction people without osteoporosis and osteonecrosis history (comparison cohort). All study subjects were followed from the date of their dental extraction (index date) to the development of ONJ and were included in the study up to 2011 or were lost to the study, whichever occurred first. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence intervals for the two cohorts. Patients with osteoporosis had a significantly higher risk to develop ONJ than healthy persons (adjusted HR, 2.05; 95% confidence interval, 1.58–2.65). The risk of ONJ increased with the severity of osteoporosis, no matter whether patient with cancer or not. A cumulative effect of dental extraction frequency may increase the risk of ONJ. We concluded that ONJ is caused by a number of factors. Osteoporosis and past dental history play the very important roles, while BPs play the synergistic effect.

The aim of this study was to investigate the association of different dental prophylactic modalities and osteoradionecrosis (ORN) and determine the risk of ORN under different timing periods of scaling, with the use chlorhexidine mouth rinse after surgery and with different strategies of fluoride gel application in head and neck cancer (HNC) participants. A cohort of 18,231 HNC participants, including 941 ORN patients and 17,290 matched control cases, were enrolled from a Longitudinal Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) in Taiwan. Based on different dental prophylactic modalities before radiotherapy, including chlorhexidine mouth rinse, scaling, and fluoride gel, all HNC subjects were stratified into different groups. The Cox proportional hazard regression was used to compare ORN incidences under different dental prophylactic modalities. The results revealed that scaling and chlorhexidine mouth rinse were significantly related to ORN risk (P = 0.004 and P < 0.0001). Chlorhexidine mouth rinse was highly correlated to ORN occurrence (hazard ratio [HR], 1.83–2.66), as exposure increased the risk by 2.43-fold among oral cancer patients, regardless of whether they had received major oral surgery or not. Oral cancer patients receiving scaling within 2 wk before radiotherapy increased their incidence of ORN by 1.28-fold compared with patients who had not undergone scaling within 6 mo. There is no significance of fluoride application for dental prophylaxis in increasing ORN occurrence. In conclusion, dental prophylaxis before radiotherapy is strongly correlated to ORN in HNC patients. Chlorhexidine exposure and dental scaling within 2 wk before radiotherapy is significantly related to ORN risk, especially in oral cancer patients. The use of 1.1% NaF topical application did not significantly increase the risk of ORN in HNC patients. An optimal dental prophylaxis protocol to reduce ORN should concern cancer location, cautious prescription of chlorhexidine mouth rinse, and proper timing of scaling.