Malignant transformation of oral potentially malignant disorders in males: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Oral squamous cell carcinoma could be preceded by clinically evident oral potentially malignant disorders (OPMDs). Transformation of OPMDs to cancer has been studied in several population groups. It is difficult to undertake comparisons across populations due to variations in the methods of computation of malignancy rates among different studies. The aim of our study was to estimate the rate of malignant transformation of OPMDs taking into account the duration of follow-up and to identify the significant factors indicative of malignant potential.</p> <p>Methods</p> <p>A total of 148 male patients with OPMDs were included. They were selected among all consecutive subjects registered at the maxillofacial clinic at a medical hospital in Kaohsiung, Taiwan. The mean follow up period was 37.8 months.</p> <p>Results</p> <p>The malignant transformation rate was highest in subjects diagnosed with oral epithelial dysplasia. In this group the transformation rate was 7.62 per 100 persons-year. The rate in the group with verrucous hyperplasia (VH) was 5.21 per 100 persons-year, and in those with hyperkeratosis or epithelial hyperplasia was 3.26 per 100 persons-year. The anatomical site of OPMDs was the only statistically significant variable associated with malignancy. The hazard rate ratio (HRR) was 2.41 times for tongue lesions when compared with buccal lesions.</p> <p>Conclusion</p> <p>The reported discrepancies of malignant transformation of OPMDs involve the follow-up time to cancer development and hence it is preferable to use a time-to-event estimation for comparisons. We found that malignant transformation of OPMDs involving the tongue was significantly higher than in other anatomical subsites after adjusting for the clinicopathological type or lifestyle factors at diagnosis.</p

Splint therapy for disc displacement with reduction of the temporomandibular joint. Part I: Modified mandibular splint therapy

AbstractThe aims of this preliminary study were to present a modified mandibular splint together with a treatment regimen and to evaluate their effects on the treatment of reciprocal joint sounds of the temporomandibular joint (TMJ). The study participants were recruited from 312 consecutive patients in the temporomandibular disorder clinic of a medical center in Taiwan from January 2003 to December 2003. From among these, 59 cases with typical reciprocal clicking were selected for this study. All participants were treated with a modified mandibular splint and then followed up for 6 months. Successful treatment was defined as leading to the disappearance of the joint sounds of TMJ, as described by patients. Based on clinical evaluation, the overall success rate was 71.2% (42/59) with minimal temporary complications. Patients with clicking at less than 3.5cm of interincisal opening had a success rate of 92.5%, which was higher than the success rate of patients with clicking at a mouth opening of 3.5cm or more. This study showed that a modified mandibular splint can be used to treat reciprocal clicking of the TMJ effectively and encouraged us to conduct further study on the efficacy of this splint to treat disc displacement with reduction of TMJ using magnetic resonance imaging examination

Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression

Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity

Blockchain-Based Medical Record Management with Biofeedback Information

Blockchain is a new emerging technology of distributed databases, which guarantees the integrity, security and incorruptibility of data by means of the cryptography. Such features are suitable for secure and reliable data storage. This chapter investigates the blockchain-based architecture with applications to medical health record or biofeedback information management. This framework employs the smart contract to establish a medical record management system to ensure the privacy of patients. Moreover, the blockchain technique accelerates the medical record or information exchange such that the cost of human resource is significant reduced. All patients can manage their individual medical records and information easily in the different hospitals and clinics. They also have the privilege to deal with and authorize personal medical records in the proposed management framework

A Combined DNA-Affinic Molecule and N-Mustard Alkylating Agent Has an Anti-Cancer Effect and Induces Autophagy in Oral Cancer Cells

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC50 in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future

Triclosan Disrupts SKN-1/Nrf2- Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells

Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Transculturalization of a Diabetes-Specific Nutrition Algorithm: Asian Application

The prevalence of type 2 diabetes (T2D) in Asia is growing at an alarming rate, posing significant clinical and economic risk to health care stakeholders. Commonly, Asian patients with T2D manifest a distinctive combination of characteristics that include earlier disease onset, distinct pathophysiology, syndrome of complications, and shorter life expectancy. Optimizing treatment outcomes for such patients requires a coordinated inclusive care plan and knowledgeable practitioners. Comprehensive management starts with medical nutrition therapy (MNT) in a broader lifestyle modification program. Implementing diabetes-specific MNT in Asia requires high-quality and transparent clinical practice guidelines (CPGs) that are regionally adapted for cultural, ethnic, and socioeconomic factors. Respected CPGs for nutrition and diabetes therapy are available from prestigious medical societies. For cost efficiency and effectiveness, health care authorities can select these CPGs for Asian implementation following abridgement and cultural adaptation that includes: defining nutrition therapy in meaningful ways, selecting lower cutoff values for healthy body mass indices and waist circumferences (WCs), identifying the dietary composition of MNT based on regional availability and preference, and expanding nutrition therapy for concomitant hypertension, dyslipidemia, overweight/obesity, and chronic kidney disease. An international task force of respected health care professionals has contributed to this process. To date, task force members have selected appropriate evidence-based CPGs and simplified them into an algorithm for diabetes-specific nutrition therapy. Following cultural adaptation, Asian and Asian-Indian versions of this algorithmic tool have emerged. The Asian version is presented in this report

Effect of P to A Mutation of the N-Terminal Residue Adjacent to the Rgd Motif on Rhodostomin: Importance of Dynamics in Integrin Recognition

Rhodostomin (Rho) is an RGD protein that specifically inhibits integrins. We found that Rho mutants with the P48A mutation 4.4–11.5 times more actively inhibited integrin α5β1. Structural analysis showed that they have a similar 3D conformation for the RGD loop. Docking analysis also showed no difference between their interactions with integrin α5β1. However, the backbone dynamics of RGD residues were different. The values of the R2 relaxation parameter for Rho residues R49 and D51 were 39% and 54% higher than those of the P48A mutant, which caused differences in S2, Rex, and τe. The S2 values of the P48A mutant residues R49, G50, and D51 were 29%, 14%, and 28% lower than those of Rho. The Rex values of Rho residues R49 and D51 were 0.91 s−1 and 1.42 s−1; however, no Rex was found for those of the P48A mutant. The τe values of Rho residues R49 and D51 were 9.5 and 5.1 times lower than those of P48A mutant. Mutational study showed that integrin α5β1 prefers its ligands to contain (G/A)RGD but not PRGD sequences for binding. These results demonstrate that the N-terminal proline residue adjacent to the RGD motif affect its function and dynamics, which suggests that the dynamic properties of the RGD motif may be important in Rho's interaction with integrin α5β1

The p12 Domain Is Unstructured in a Murine Leukemia Virus p12-CAN Gag Construct

The Gag polyproteins of gammaretroviruses contain a conserved p12 domain between MA and CA that plays critical roles in virus assembly, reverse transcription and nuclear integration. Here we show using nuclear magnetic resonance, that p12 is unstructured in a Moloney murine leukemia virus (MMLV) Gag fragment that includes the N-terminal domain of CA (p12-CAN). Furthermore, no long range interactions were observed between the domains, as has been previously predicted. Flexibility appears to be a common feature of Gag “late” domains required for virus release during budding. Residues near the N-terminus of CAN that form a β-hairpin in the mature CA protein are unfolded in p12-CAN, consistent with proposals that hairpin formation helps trigger capsid assembly