Periodontitis is one of the most prevalent inflammatory diseases, characterized by gingival inflammation and alveolar bone loss. MicroRNAs (MiRNAs) are important regulators of inflammation and involved in periodontitis pathogenesis. In this work, we studied the roles of microRNA-21 (miR-21) in periodontitis. MiR-21 is up-regulated in both periodontitis patients and the mice that induced with periodontitis. We tested the roles of miR-21 in the macrophages challenged by periodontitis pathogen Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). MiR-21 expression is up-regulated in P. gingivalis LPS-stimulated macrophages. MiR-21 mimic inhibits the pro-inflammatory cytokine production by macrophages, while miR-21 deficiency elevates the production of pro-inflammatory cytokines. Moreover, absence of miR-21 promotes activation of nuclear factor-κB (NF-κB) in P. gingivalis LPS- stimulated cells. In a murine periodontitis model, ligation induced exacerbated gingival inflammation and alveolar bone loss in miR-21 deficient mice than their wild-type littermates. These results demonstrated the anti-inflammatory function of miR-21 in vitro and in vivo, indicating miR-21 could be an interventional target for the control of periodontitis.
Pregnancy is a special period marked with complicated changes in various immune responses. Although pregnant women are prone to developing gingival inflammation, its immunological mechanism remains to be clarified. In a modified ligature-induced periodontal disease murine model, pregnant mice developed more severe alveolar bone loss. Using this model, we investigated the Treg responses during exacerbated periodontal disease in pregnant mice. We tested Tregassociated molecules in gingival tissues by quantitative real-time PCR and found decreased gingival expression of Foxp3, TGFβ, CTLA-4, and CD28 in pregnant mice after periodontal disease induction. We further confirmed that lower number of Treg cells were present in the cervical lymph nodes of pregnant periodontitis mice. Treg cells from the cervical lymph nodes of ligated pregnant mice and non-pregnant mice were tested for their suppressive function in vitro. We manifested that Treg suppressive function was also down-regulated in the pregnant mice. Additionally, we demonstrated that more inflammatory Th17 cells were present in the cervical lymph nodes of ligated pregnant mice. Therefore, impaired Treg development and function, together with upregulated Th17 response, may contribute to the exacerbated periodontal disease during pregnancy.
Although pregnant women are prone to gingival inflammation, its mechanism remains unclear. Animal models are ideal for investigating immunological mechanisms in the periodontal disease. A murine model for ligature-induced periodontal disease has been modified and utilized to determine the susceptibility to periodontal inflammation and tissue damage in pregnant mice. Expression of different inflammatory mediators in the gingivae was determined by quantitative real-time PCR (qPCR). Inflammatory bone loss was determined by measuring the distance from the cementoenamel junction to the alveolar bone crest (CEJ-ABC). Oral bacterial number was determined by the CFU (Colony Forming Units) count from anaerobic culture of oral swabs. In our experiments, ligation itself did not cause higher gingival inflammation and bone loss in pregnant mice than non-pregnant mice, while ligation combined with P. gingivalis infection led to increased gingival inflammation and periodontal bone loss, accompanied by lower gingival expression of anti-inflammatory cytokines in pregnant mice. Our results indicated that P. gingivalis infection was important in inducing more severe periodontal diseases during pregnancy, which might be attributed to the down-regulated anti-inflammatory mechanisms, but not be associated with higher oral bacterial burden.
77 Background: Terminally ill cancer patients have complex medical and psychosocial needs at the end of life. Given these complexities, limited data is available to suggest the appropriate timing of palliative care involvement in the treatment of cancer. Our study aims to describe the referral patterns of inpatient palliative care consultations in advanced cancer patients in a tertiary care center. Methods: A retrospective review was performed. Inpatient palliative consultation was obtained in cancer patients from January 1, 2014 to December 31, 2014. Descriptive statistics are used in data analysis. Results: Inpatient palliative care consults (IPCC) were obtained for 245 cancer patients admitted to Saint Louis University Hospital. Of the 245, 130 were male (53.06%), 115 were female (46.93%), 128 were White (52.24%), and 114 were Black (46.53%). Newly diagnosed patients with cancer during the current admission were 79(32.24%). 57 (23.26%) patients were admitted to the Intensive care unit during hospitalization. A total of 39(15.91%) patients died in the hospital; among those who died in the hospital 34 had ICU stay during the hospitalization or died in the ICU (87%). Malignancies most common were lung 71(28.97%) followed by pancreatic-biliary 33(13.4%), lymphoma and leukemia 22(8.9%), hepatocellular carcinoma 18(7.34%), head and neck 16 (6.5%), and upper GI 16 (6.5%). Disposition at discharge included home hospice 67 (28.3%), hospice in facility 27(11%), home without hospice 71(28.9%), facility without hospice 39(15.9%). Conclusions: According to the National Hospice and Palliative Care Organization as of 2013, 7.0% hospice patients die in acute care hospitals. Our data shows 15.9% who received IPCC died in the hospital with 87% dying in ICU. This is likely due to delays in the initiation of palliative care consultation as outpatient leading to increase strain on tertiary referral centers. In another study 22% of eligible Black patients received IPCC. Our rate of IPCC in Blacks was 46.5%. This highlights the disparity in access to outpatient palliative care in this population. Future efforts should be made to promote early outpatient palliative services to reduce ICU admissions, hospital re-admissions and healthcare costs.
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