Lemierre Syndrome associated with dental infections : report of one case and review of the literature

The first publication on Lemierre Syndrome appears in 1936 by Lemierre. It is defined as an ?oropharynx bacterial infection characterized by the thrombophlebitis in the internal jugular vein, derived in a systemic septic embolism?. In 81% of the cases, the Fusobacterium necrophorum is the most frequent etiologic agent. Fever is the most common symptom, but it can depending on the primary infection, tonsillitis, mastoiditis or odontogenic infection. According to the literature the mortality is very low, but with a significant morbidity, that is why the diagnosis and early treatment is very important. The diagnosis it´s clinical, even though the CT scan and other diagnosis methods (echography, MRI) help to determine the extent of the infection. It?s necessary to administrate the antibiotics endovenous at high dose, (keeping in mind that the most frequent micro organism is anaerobic), and vital support measures if neccessary. We present a case report of Lemierre Syndrome associated to an odonthogenic infection caused by the 4.8 molar

Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1–5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2–CD44–SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state

Nutrient supply affects the mRNA expression profile of the porcine skeletal muscle

Background: The genetic basis of muscle fat deposition in pigs is not well known. So far, we have only identified a limited number of genes involved in the absorption, transport, storage and catabolism of lipids. Such information is crucial to interpret, from a biological perspective, the results of genome-wide association analyses for intramuscular fat content and composition traits. Herewith, we have investigated how the ingestion of food changes gene expression in the gluteus medius muscle of Duroc pigs. Results: By comparing the muscle mRNA expression of fasted pigs (T0) with that of pigs sampled 5 h (T1) and 7 h (T2) after food intake, we have detected differential expression (DE) for 148 (T0-T1), 520 (T0-T2) and 135 (T1-T2) genes (q-value of 1.5). Many of these DE genes were transcription factors, suggesting that we have detected the coordinated response of the skeletal muscle to nutrient supply. We also found DE genes with a dual role in oxidative stress and angiogenesis (THBS1, THBS2 and TXNIP), two biological processes that are probably activated in the post-prandial state. Finally, we have identified several loci playing a key role in the modulation of circadian rhythms (ARNTL, PER1, PER2, BHLHE40, NR1D1, SIK1, CIART and CRY2), a result that indicates that the porcine muscle circadian clock is modulated by nutrition. Conclusion: We have shown that hundreds of genes change their expression in the porcine skeletal muscle in response to nutrient intake. Many of these loci do not have a known metabolic role, a result that suggests that our knowledge about the genetic basis of muscle energy homeostasis is still incomplete

Development of three-dimensional tissue engineered bone-oral mucosal composite models

Tissue engineering of bone and oral mucosa have been extensively studied independently. The aim of this study was to develop and investigate a novel combination of bone and oral mucosa in a single 3D in vitro composite tissue mimicking the natural structure of alveolar bone with an overlying oral mucosa. Rat osteosarcoma (ROS) cells were seeded into a hydroxyapatite/tri-calcium phosphate scaffold and bone constructs were cultured in a spinner bioreactor for 3 months. An engineered oral mucosa was fabricated by air/liquid interface culture of immortalized OKF6/TERET-2 oral keratinocytes on collagen gel-embedded fibroblasts. EOM was incorporated into the engineered bone using a tissue adhesive and further cultured prior to qualitative and quantitative assessments. Presto Blue assay revealed that ROS cells remained vital throughout the experiment. The histological and scanning electron microscope examinations showed that the cells proliferated and densely populated the scaffold construct. Micro computed tomography (micro-CT) scanning revealed an increase in closed porosity and a decrease in open and total porosity at the end of the culture period. Histological examination of bone-oral mucosa model showed a relatively differentiated parakeratinized epithelium, evenly distributed fibroblasts in the connective tissue layer and widely spread ROS cells within the bone scaffold. The feasibility of fabricating a novel bone-oral mucosa model using cell lines is demonstrated. Generating human ‘normal’ cell-based models with further characterization is required to optimize the model for in vitro and in vivo applications