Risk factors and prognosis for the primary intraosseous carcinoma of the jaw.

Primary intraosseous carcinoma (PIOC) is a rare but aggressive type of odontogenic tumour arising within the jawbone. Diagnosis criteria and treatment strategy remain difficult and controversial. The present study aimed to clarify the clinicopathological features and determine prognostic factors in management of PIOC. A retrospective study of 30 patients with PIOC, treated at the Hospital of Stomatology of Sun Yat-sen University between 2009 and 2017, was conducted. Clinical, histopathological and treatment modality data were collected. Follow-up data were recorded to determine prognostic factors. There were 19 males and 11 females with a mean age of 52.3 years. The most common location of the tumour was the mandible (90%). Having a history of tooth extraction or tooth mobility was the major characteristic symptom (63.3%), jaw swelling coming in second (53.3%). Half of the patients underwent surgery alone. The estimated 2-year overall survival rate (OS) and recurrence-free survival rate (RFS) were 61.3% and 40.1%, respectively. Higher histological grade was an independent risk factor for poor OS (hazard ratio (HR) 0.233 [0.059-0.915], P=0.037), while at pN+ stage for RFS, HR=5.627 [1.199-26.409], P=0.029. Because of its rarity and intrabony site, the classification, staging and treatment guidelines for PIOC should be further studied and established.

PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway

This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males). Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6), type ΙΙ procollagen gene (COL2A1), cartilage oligomeric matrix protein (COMP), aggrecan (AGC1), type ΙX procollagen gene (COL9A2) and collagen type 1 alpha 1 (COL1A1) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The expressions of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and extracellular regulated protein kinase (ERK) were measured. Overexpressing PDK2 promoted cell viability, adhesion and inhibited cell migration in MSCs (all P<0.05). qRT-PCR assay showed a potent increase in the mRNA expressions of all chondrogenesis markers in response to overexpressing PDK2 (P<0.01 or P<0.05). PDK2 overexpression also induced a significant accumulation in mRNA and protein expressions of JNK, p38MAPK and ERK in MSCs compared to the control (P<0.01 or P<0.05). Meanwhile, silencing PDK2 exerted the opposite effects on MSCs. This study shows a preliminary positive role and potential mechanisms of PDK2 in chondrogenic differentiation of MSCs. It lays the theoretical groundwork for uncovering the functions of PDK2 and provides a promising basis for repairing cartilage lesions in osteoarthritis.

The determinations of nucleosome positioning.

OBJECTIVE: Nucleosomes are the basic packaging units of chromatin, determinants of nucleosome organization playing a major role in genome packaging. Although a wide variety of nucleosome organization factors have been considered separately across the whole or partial human genomic regions, it is unclarified that what the major determinants and their roles in scale are when being put all together. And it is also unknown that what the similarities and differences of determinants between different genomic features such as genes of different expression levels or genomic regions with different functions. MATERIALS AND METHODS: We detected commonalities and characteristics of nucleosome positioning determinants in different genes and regions with 1591486 nucleosomes identified by ourselves in human CD4+ cell. RESULTS: It was found that a distinct linear combination of about 20 nucleosome-positioning factors explained nucleosome occupancy for each genomic feature. In those linear combinations, 6 DNA sequence attributes (Roll stiffness and Twist stiffness, CT and AG, CG and shift stiffness) and a histone modification (H4R3me2) are shared. And other factors are varied. Roll stiffness and Twist stiffness are the most important features. They are dominant, alone explaining 96.61-98.45% of the positioning weight in each genomic feature. The characteristic factors in each combination are larger in number, but weaker in power. Numerous histone modifications play a subtle role for nucleosome positioning. CONCLUSIONS: The present study provides a more accurate positioning nucleosome-map with higher resolution and a dramatically simplified means to predict and understand intrinsic nucleosome occupancy in different genomic features in human CD4+ cell. Roll stiffness and Twist stiffness are the two most important determinants in all genomic features. They may dominate because they both determine the degree of DNA bending and correlates with many other DNA structural characteristics. Histone modifications play a role of subtle allocation for nucleosome occupancy.