FASN inhibition sensitizes metastatic OSCC cells to cisplatin and paclitaxel by downregulating cyclin B1.

OBJECTIVES: To investigate the potential effect of fatty acid synthase (FASN) inhibitor orlistat to enhance the effectiveness of chemotherapy drugs widely used to treat oral squamous cell carcinomas (OSCC), such as 5-fluorouracil, cisplatin, and paclitaxel. METHODS: The OSCC SCC-9 LN-1 metastatic cell line, which expresses high levels of FASN, was used for drug combination experiments. Cell viability was analyzed by crystal violet staining and automatic cell counting. Apoptosis and cell cycle were analyzed by flow cytometry with Annexin-V/7-AAD and propidium iodide staining, respectively. Cyclin B1, Cdc25C, Cdk1, FASN, and ERBB2 levels were assessed by Western blotting. Finally, cell scratch and transwell assays were performed to assess cell migration and invasion. RESULTS: Inhibition of FASN with orlistat sensitized SCC-9 LN-1 cells to the cytotoxic effects of paclitaxel and cisplatin, but not 5-fluorouracil, which was accompanied by a significant reduction in cyclin B1. The suppression of proliferation, migration, and invasion of SCC-9 LN-1 cells induced by orlistat plus cisplatin or paclitaxel was not superior to the effects of chemotherapy drugs alone. CONCLUSION: Our results suggest that orlistat enhances the chemosensitivity of SCC-9 LN-1 cells to cisplatin and paclitaxel by downregulating cyclin B1.

Alpha-terpineol complexed with beta-cyclodextrin reduces damages caused by periodontitis in rats.

BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS: The treatment with αTPN-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION: The results obtained suggest that the treatment with αTPN-ßCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-ßCD.

Periodontitis causes abnormalities in the liver of rats.

BACKGROUND: Periodontitis not only causes injury to the periodontium, but also damages other tissues such as: articulate, renal, cardiac, and hepatic. The objective of this study was to investigate periodontitis induced alterations in liver function and structure using an experimental model. METHODS: Twenty female rats (Rattus norvegicus) were allocated into two groups: control and periodontitis. Gingival bleeding index and oxidative stress parameters and specific circulating biomarkers were measured. Immunohistochemistry was carried out using alkaline phosphatase (AlkP) staining of the liver. Hepatic tissues, cytokines, and lipid contents were measured. Histopathologic evaluation of the liver was carried out using light and electron microscopy. RESULTS: Liver histopathologic and immunohistochemistry assessment showed increase in steatosis score, and presence of binucleate hepatocytes and positive cells for AlkP in periodontitis versus control group. Ultrastructural evaluation showed significant increase in size and number of lipid droplets (LD), distance between the cisterns of rough endoplasmic reticulum (RER), mitochondria size, foamy cytoplasm, and glycogen accumulation in the liver of the periodontitis group compared with the control group. In addition, plasma levels of AlkP, high-density lipoprotein (HDL), triglycerides, and total cholesterol were also changed. CONCLUSION: Experimental periodontitis caused immunohistochemistry, histopathologic, ultrastructural, oxidative, and biochemical changes in the liver of rats.

Microbiological, lipid and immunological profiles in children with gingivitis and type 1 diabetes mellitus.

OBJECTIVE: The aim of this study was to compare the prevalence of periodontal pathogens, systemic inflammatory mediators and lipid profiles in type 1 diabetes children (DM) with those observed in children without diabetes (NDM), both with gingivitis. MATERIAL AND METHODS: Twenty-four DM children and twenty-seven NDM controls were evaluated. The periodontal status, glycemic and lipid profiles were determined for both groups. Subgingival samples of periodontal sites were collected to determine the prevalence of periodontal microorganisms by PCR. Blood samples were collected for IL-1-ß, TNF-α and IL-6 analysis using ELISA kits. RESULTS: Periodontal conditions of DM and NDM patients were similar, without statistical differences in periodontal indices. When considering patients with gingivitis, all lipid parameters evaluated were highest in the DM group; Capnocytophaga sputigena and Capnocytophaga ochracea were more prevalent in the periodontal sites of DM children. "Red complex" bacteria were detected in few sites of DM and NDM groups. Fusobacterium nucleatum and Campylobacter rectus were frequently found in both groups. Similar levels of IL-1-ß, TNF-α and IL-6 were detected in DM and NDM children. CONCLUSION: Clinical and immunological profiles are similar between DM and NDM children. The presence of Capnocytophaga sputigena and Capnocytophaga ochracea were associated with gingivitis in DM children.

Microbiological, lipid and immunological profiles in children with gingivitis and type 1 diabetes mellitus

Abstract Objective The aim of this study was to compare the prevalence of periodontal pathogens, systemic inflammatory mediators and lipid profiles in type 1 diabetes children (DM) with those observed in children without diabetes (NDM), both with gingivitis. Material and methods Twenty-four DM children and twenty-seven NDM controls were evaluated. The periodontal status, glycemic and lipid profiles were determined for both groups. Subgingival samples of periodontal sites were collected to determine the prevalence of periodontal microorganisms by PCR. Blood samples were collected for IL-1-β, TNF-α and IL-6 analysis using ELISA kits. Results Periodontal conditions of DM and NDM patients were similar, without statistical differences in periodontal indices. When considering patients with gingivitis, all lipid parameters evaluated were highest in the DM group; Capnocytophaga sputigena and Capnocytophaga ochracea were more prevalent in the periodontal sites of DM children. “Red complex” bacteria were detected in few sites of DM and NDM groups. Fusobacterium nucleatum and Campylobacter rectus were frequently found in both groups. Similar levels of IL-1-β, TNF-α and IL-6 were detected in DM and NDM children. Conclusion Clinical and immunological profiles are similar between DM and NDM children. The presence of Capnocytophaga sputigena and Capnocytophaga ochracea were associated with gingivitis in DM children.

The role of immune system in the development of periodontal disease: a brief review / O papel do sistema imune no desenvolvimento da doença periodontal: uma breve revisão

Periodontitis is a highly complex and multi-factorial disease. This review summarizes some immunological factors involved in the development and control of this oral disease, such as: the participation of inflammatory cells in local inflammation, the synthesis of chemotaxis proteins with activation of the complement system and a range of antimicrobial peptides, such as defensins, cathelicidin and saposins. The integration of pathogen-associated molecular patterns (PAMPs) from microorganisms with their surface receptors in the immune cells, induces the production of several cytokines and chemokines that presents either a pro- and/or anti-inflammatory role by stimulating the secretion of a great variety of antibody subtypes and the activation of mechanisms of controlling the disease, such as the regulatory T cells. Although several studies have tried to clarify some of the immune mechanisms involved in periodontal disease, more studies must be conducted to understand its development and progression and consequently to discover new alternatives for the prevention and treatment of this severe inflammatory disease.

A periodontite é uma doença altamente complexa e multifatorial. Esta breve revisão reúne alguns fatores imunológicos envolvidos no desenvolvimento e controle desta doença oral, tais como: a participação de células inflamatórias no local da inflamação, a síntese de proteínas quimiotáticas através da ativação do sistema complemento e a presença de alguns dos peptídeos antimicrobianos, como defensinas, catelicidinas e saposinas. A interação de padrões moleculares associados à patógenos (PAMPs) de microrganismos com seus receptores de superfície, em células imunológicas, induz a produção de várias citocinas e quimiocinas que apresentam função pró- e/ou anti-inflamatória estimulando a secreção de uma grande variedade de subtipos de anticorpos e a ativação de mecanismos de controle da doença, como as células T reguladoras. Embora vários trabalhos tentem esclarecer alguns dos mecanismos imunológicos envolvidos na doença periodontal, estudos adicionais são necessários para ampliar conhecimentos sobre o desenvolvimento, a progressão e, consequentemente, para se descobrir novas alternativas de prevenção e tratamento desta grave doença inflamatória.

The effects of nicotine and cotinine on Porphyromonas gingivalis colonisation of epithelial cells.

Smoking is a risk factor for development of periodontitis. Porphyromonas gingivalis is an important colonizer of the subgingival crevice and is a major pathogenic agent in the initiation and progression of severe forms of periodontal disease. However, the effect of major cigarette's derivatives on P. gingivalis is poorly understood. The purpose of this study was to determine the influence of nicotine and cotinine on bacterial colonisation to epithelial cells. KB cells monolayers and P. gingivalis ATCC 33277 were exposed to 0.1, 10 and 100 microg/mL of nicotine and cotinine concentrations. The epithelial cells were incubated for 24 h while P. gingivalis was exposed to these substances until reach early logarithmic phase. After the incubation period, P. gingivalis ability to colonize KB cells was assayed. The number of cell-associated/invasive bacteria was assessed by counting the colony-forming units. 100 microg/mL cotinine significantly increased P. gingivalis association and invasion of epithelial cells, when the bacteria was exposed to this substance (p<0.05; ANOVA-Tukey test). No other condition or drug altered the bacteria colonisation ability (p>0.05). These data indicated that cotinine may interfere with P. gingivalis ability to associate and invade the epithelial cells. Further studies are needed to investigate whether oral cells might be more susceptible to be colonized by P. gingivalis in smokers.

Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection.

The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-alpha, interferon-gamma, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.