Oral squamous cell carcinoma (OSCC) in the background of oral submucous fibrosis (OSF) caused by areca nut chewing has a high incidence in Asia-Pacific countries. However, the molecular mechanism remains unclear. Here, we performed circRNA microarray analysis to screen the circRNA expression profiles in OSCC and OSF. We identified circEPSTI1 as a circRNA with consistent, sequential upregulation from normal buccal mucosa (NBM) to OSF to OSCC. Functionally, circEPSTI1 significantly promoted OSCC cell proliferation and invasion, as evidenced by the CCK8, colony formation, wound healing, and transwell assays with circEPSTI1 overexpression and silencing. OSCC patients with circEPSTI1 high status exhibited poor prognoses. CircEPSTI1 sponged miR-942-5p and accelerated epithelialmesenchymal transition (EMT) to increase LTBP2 expression in OSCC through phosphorylation of PI3K/Akt/mTOR signaling pathway components. Blocking the PI3K/Akt/mTOR signaling pathway with the dual PI3k/mTOR inhibitor BEZ235 reversed OSCC progression induced by overexpression of circEPSTI1 and LTBP2. Collectively, these results indicate that the circEPSTI1/miR-942-5p/LTBP2 axis affects OSCC cell proliferation and invasion via the acceleration of EMT and the phosphorylation of PI3K/Akt/mTOR signaling pathway components. CircEPSTI1 may be an independent diagnostic and prognostic marker and a potential therapeutic target for OSCC patients with OSF.

Cellular tropism of vaccinia virus (VACV) isVaccinia virus (VACV) is the prototypical member of the poxvirus family of large, complex, double-stranded DNA viruses (21). VACV has a very broad host range and is capable of infecting many vertebrate animal species. Its host range, however, can be significantly narrowed by deleting from its genome some of the so-called host range genes, the most important of which are E3L, K1L, and C7L (17). VACV mutants deleted of E3L (⌬E3L) or both K1L and C7L (⌬K1L⌬C7L) replicate abortively and express only a subset of viral genes in most mammalian cell lines (3, 24). These mutants are highly attenuated in animal hosts but are capable of eliciting immune responses, making them attractive vaccine vectors for infectious diseases and cancers (27,28). NYVAC, a VACV strain derived through deletion of 18 genes, including both K1L and C7L (27), has been used as the vector for an AIDS vaccine (2).The functions of E3L and the host factors that restrict the replication of the ⌬E3L mutant have been studied extensively. E3L encodes a 20-kDa and a 25-kDa protein that bind doublestranded RNA (dsRNA) and Z form DNA (6, 15). The E3 proteins antagonize the dsRNA-dependent protein kinase PKR (5), which exists as an inactive form in the cells and undergoes autophosphorylation and activation upon binding to dsRNA. The activated PKR phosphorylates the ␣ subunit of eukaryotic initiation factor 2 (eIF2␣), resulting in a block in protein translation at the initiation step. The infection of most mammalian cells by the ⌬E3L mutant leads to the activation of PKR and a block in translating viral mRNAs (16). The replication of the ⌬E3L mutant in nonpermissive HeLa cells can be rescued by silencing PKR expression (32), while its replication in permissive Huh7 (human hepatoma) cells can be blocked by upregulating PKR expression with interferon (IFN) treatment (1). In addition to affecting PKR, E3 has also been shown to inactivate IFN-stimulated gene 15 (ISG15) (14), another IFN effector that plays a role in host defense against VACV.Like the replication of the ⌬E3L mutant, the replication of the ⌬K1L⌬C7L mutant in nonpermissive HeLa cells is blocked at the translation of viral mRNA. However, the host factors that restrict the replication of the ⌬K1L⌬C7L mutant and the molecular functions of K1L or C7L remain a mystery. K1 and C7 share no amino acid sequence homology, but either K1L or C7L can complement the replication defect of the ⌬K1L⌬C7L mutant in most cell lines. The exception is rabbit RK13 cells, where K1L but not C7L can complement (24). K1L is present in only a few orthopoxviruses, while C7L or a functional homologue of C7L is present in almost all mammalian poxviruses (18). K1 comprises multiple ankyrin repeats, a protein motif that is involved in protein-ligand interaction. It was shown to prevent the degradation of IB␣ and to thus inhibit host . C7L has no homologue outside the poxvirus family, and its molecular function remains unknown. It may play a role in inhibiting cellular apoptosis in respons...

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Recent studies have shown that substance dependence (addiction) is accompanied with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and betel quid dependence (BQD)-related physiopathological characteristics still remain unclear. Resting-state functional magnetic resonance imaging images were obtained from 26 BQD individuals and 28 matched healthy control subjects. Group independent component analysis was performed to analyze the resting state images into spatially independent components. Gray matter volume was examined as covariate with voxel-based morphometry to rule out its effect on the functional results. The severity of BQD was assessed by the BQD Scale (BQDS). We observed decreased functional connectivity in anterior part of the DMN including ventral medial prefrontal cortex, orbital MPFC (OMPFC)/anterior cingulate cortex (ACC). Furthermore, the functional connectivity within the OMPFC/ACC in BQD individuals was negatively correlated with BQDS (p = 0.01, r = -0.49). We reported decreased functional connectivity within anterior part of the DMN in BQD individuals, which provides new evidence for the role of the DMN in the pathophysiology of BQD.

Oral submucous fibrosis (OSF) is a potentially malignant disease predominantly found in Asian people. The areca nut has been implicated in this disease. Arecoline, one of the areca alkaloids, induces epithelial-mesenchymal transition (EMT)-related factors in primary human buccal mucosal fibroblasts. Yet, the mechanisms of the underlying arecoline-induced EMT in OSF remain unknown. In the present study, we aimed to investigate the role of microRNAs (miRNAs) in arecoline-induced EMT in HaCaT cells. We found that miR-203 was significantly downregulated in OSF tissues compared to that in normal buccal mucosa tissues, and that miR-203 negatively regulated secreted frizzled-related protein 4 (SFRP4) and positively regulated transmembrane-4 L six family member 1 (TM4SF1). We observed that upregulation of miR-203 significantly decreased the cell proliferation of HaCaT cells, and significantly upregulated the expression of cytokeratin 19 (CK19) and E-cadherin proteins, whereas it significantly downregulated the expression of N-cadherin and vimentin compared to these levels in the vehicle control cells. Thus, we provide evidence to illustrate that miR-203 plays a role in the pathogenesis of OSF, which may be a target for OSF management.

Background: Betel quid is the fourth most popular psychoactive agent worldwide. Neuroimaging studies have suggested betel-quid dependence is accompanied by abnormality in brain structure and function. However, the neural correlates of executive function deficit and prefrontal cortical thickness associated with betel-quid chewing still remain unclear. Objective: The present study aimed to examine the relationship between executive function deficit and prefrontal cortical thickness in chronic betelquid chewers. Methods: Twenty-three betel-quid-dependent chewers and 26 healthy controls were recruited to participate in this study. Executive function was tested using three tasks. Cortical thickness analysis was analyzed with the FreeSurfer software package. Results: Behavioral results suggested a profound deficit of executive function in betel-quid-dependent chewers. Cortical thickness analysis revealed thinner cortex in the bilateral dorsolateral prefrontal cortex in betel-quid-dependent chewers. Further analysis suggested that cortical thickness of the bilateral dorsolateral prefrontal cortex mediated the correlation of betel-quid chewing and executive function. Conclusions: These results suggest the important role of executive function and cortical thickness of the dorsolateral prefrontal cortex with betel-quid chewing. Our findings provide evidence that executive function deficit may be mediated by the cortical thickness of the dorsolateral prefrontal cortex. These results could potentially help us develop novel ways to diagnose and prevent betel-quid dependence.

The results of this study suggest that mandibular segmental resections and the precise orientation of pre-bent titanium plates could be simultaneously assisted by CORPPP digital surgical guide plates. The use of these guide plates should be expanded.

Objectives The study aimed to investigate the ceRNA network in biological development of Tongue Squamous Cell Carcinoma (TSCC) and to identify novel molecular subtypes of TSCC to screen potential biomarkers for target therapy and prognosis by using integrated genomic analysis based on The Cancer Genome Atlas (TCGA) database. Material and methods Data on gene expressions were downloaded from TCGA and GEO database. Differentially expressed RNAs(DERNAs) were shown by DESeq2 package in R. Functional enrichment analysis of DEmRNAs was performed using clusterprofilers in R. PPI network was established by referring to String website. Survival analysis of DERNAs was carried out by survival package in R. Interactions among mRNAs, miRNAs and lncRNAs were obtained from Starbase v3.0 and used to construct ceRNA network. Consensus Cluster Plus package was applied to identify molecular subtypes. All key genes were validated by comparing them with GEO microarray data. Statistical analyses of clinical features among different subtypes were performed using SPSS 22.0. Results A total of 2907 mRNAs (1366 up-regulated and 1541 down-regulated), 191miRNAs (98 up-regulated and 93 down-regulated) and 1831 lncRNAs (1151 up-regulated and 680 down-regulated) were identified from tumor and normal tissues. A ceRNA network was successfully constructed and 15 DEmRNAs, 1 DEmiRNA, 2 DElncRNAs associated with prognosis were employed. Furthermore, we firstly identified 2 molecular subtypes, basal and differentiated, and found that differentiated subtype consumed less alcohol and was related to a better overall survival. Conclusion The study constructed a ceRNA network and identified molecular subtypes of TSCC, and our findings provided a novel insight into this intractable cancer and potential therapeutic targets and prognostic indicators.