Engineered Biomaterials Trigger Remineralization and Antimicrobial Effects for Dental Caries Restoration.

Dental caries is the most prevalent chronic disease globally, significantly impacting individuals' quality of life. A key reason behind the failure of implanted restorations is their biological inactivity, meaning they are unable to form crosslinks with the surrounding tooth structures, thus making patients susceptible to implant loss and recurrent tooth decay. For the treatment of caries, antibacterial medicine and remineralization are effective means of treating the recurrence of caries. Owing to the rapid progression in the biomaterials field, several biomaterials have been reported to display antimicrobial properties and aid in dentin remineralization. Bioactive materials hold considerable potential in diminishing biofilm accumulation, inhibiting the process of demineralization, enabling dentin remineralization, and combating bacteria related to caries. Bioactive materials, such as fluoride, amorphous calcium phosphate, bioactive glass, collagen, and resin-based materials, have demonstrated their effectiveness in promoting dentin remineralization and exerting antibacterial effects on dental caries. However, the concentration of fluoride needs to be strictly controlled. Although amorphous calcium phosphate can provide the necessary calcium and phosphorus ions for remineralization, it falls short in delivering the mechanical strength required for oral mastication. Resin-based materials also offer different advantages due to the complexity of their design. In this review, we delve into the application of advanced bioactive materials for enhancing dentin remineralization and antibacterial properties. We eagerly anticipate future developments in bioactive materials for the treatment of dental caries.

Survival Benefit of Metformin as an Adjuvant Treatment for Head and Neck Cancer: A Systematic Review and Meta-Analysis.

Background/Aims: The relationship between the efficacy of metformin and the prognosis of patients with head and neck cancer (HNC) was still unclear. This study aims to clarify the prognostic value of metformin treatment using meta-analysis. Methods: Studies related to HNC prognosis and metformin were searched in Cochrane Library, Embase, LILACS, MEDLINE and PubMed databases. A meta-analysis was performed to evaluate the association between metformin therapy and the prognosis of HNC on overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and whether article quality, comorbidities, age, region or smoking had an influence on the prognosis of metformin treatment. Pooled hazard ratio (HR) and 95% confidence interval (CI) were analyzed to assess the effect. Results: Eleven eligible studies involving 14,694 participants were included. Metformin increased the OS (HR = 0.87, 95% CI: 0.76-0.99), but failed on DFS (HR = 0.67, 95% CI: 0.40-1.09) or DSS (HR = 0.69, 95% CI: 0.41-1.14) in HNC patients. Subgroup analysis showed metformin was associated with improved OS (HR = 0.66, 95% CI: 0.49-0.88), DFS (HR = 0.49, 95% CI: 0.26-0.92) and DSS (HR = 0.38, 95% CI: 0.22-0.65) in studies with higher Newcastle-Ottawa Scale (NOS) scores. Subgroup analysis of age indicated that patients younger than 65 years (OS, HR = 0.67, 95% CI: 0.49-0.92) were more likely to benefit from metformin treatment. Subgroup analysis of comorbidities showed metformin significantly improved patient outcomes in studies without adjusted for comorbidities (OS, HR = 0.66, 95% CI: 0.51-0.85; DSS, HR = 0.38, 95% CI: 0.22-0.65), but not in studies that adjusted for comorbidities. Conclusions: Metformin improved the prognosis of HNC patients as an adjuvant therapy, especially in those with higher NOS scores. Age and comorbidities of HNC patients influenced the therapeutic effect of metformin. Further well-conducted investigations are needed.

Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

Butyrate promotes oral squamous cell carcinoma cells migration, invasion and epithelial-mesenchymal transition.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the most common type of primary malignant tumor in the oral cavity, is a lethal disease with high recurrence and mortality rates. Butyrate, a metabolite produced by periodontal pathogens, has been linked to oral diseases. The purpose of this study was to evaluate the effect of sodium butyrate (NaB) on the proliferation, migration, and invasion of OSCC cells in vitro and to explore the potential mechanism. METHODS: Two OSCC cell lines (HSC-4 and SCC-9) were treated with NaB at different concentrations. The cell proliferation was assayed by CCK-8, ethylene deoxyuridine (EdU), and flow cytometry. Wound healing and transwell assay were performed to detect cell migration and invasion. Changes in epithelial-mesenchymal transition (EMT) markers, including E-cadherin, Vimentin, and SNAI1, were evaluated by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescent staining. The expression levels of matrix metalloproteinases (MMPs) were analyzed by qRT-PCR and gelatin zymography. RESULTS: Our results showed that NaB inhibited the proliferation of OSCC cells and induced cell cycle arrest at G1 phase, but NaB significantly enhanced cell migration and invasion compared with the control group. Further mechanistic investigation demonstrated that NaB induced EMT by increasing the expression of Vimentin and SNAI1, decreasing the expression of membrane-bound E-cadherin, and correspondingly promoting E-cadherin translocation from the membrane to the cytoplasm. In addition, the overexpression of MMP1/2/9/13 was closely related to NaB treatment. CONCLUSIONS: Our study conclude that butyrate may promote the migration and invasion of OSCC cells by inducing EMT. These findings indicate that butyrate may contribute to OSCC metastasis.

Porphyromonas gingivalis outer membrane vesicles inhibit the invasion of Fusobacterium nucleatum into oral epithelial cells by downregulating FadA and FomA.

BACKGROUND: Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) participate in the formation and progression of periodontitis. They can exert virulence by invading into host cells, but the interaction between them and their specific mechanisms remain unclear. The purpose of this study was to study the effect of P. gingivalis outer membrane vesicles (OMVs) on the ability of F. nucleatum to invade oral epithelial cells, and the reasons for the influence. METHODS: The invasion abilities of the two bacteria were detected separately after mixed infection of P. gingivalis and F. nucleatum. Next, P. gingivalis OMVs were extracted with the kit, and their influence on the invasion ability of F. nucleatum was tested. The effects of P. gingivalis OMVs on F. nucleatum were evaluated by assessment of bacterial morphology, growth curves, auto-aggregation morphology, and the expression of adhesion-related proteins FadA and FomA. RESULTS: Our results showed that P. gingivalis inhibited the invasion of F. nucleatum into oral epithelial cells but F. nucleatum promoted the invasion of P. gingivalis. In subsequent experiments, we extracted P. gingivalis OMVs successfully and revealed that proteases in P. gingivalis OMVs inhibited the invasion of F. nucleatum into oral epithelial cells. Furthermore, P. gingivalis OMVs did not affect the morphology and proliferation of F. nucleatum, but proteases inside decreased the auto-aggregation of F. nucleatum. Additionally, proteases in P. gingivalis OMVs reduced the expression levels of F. nucleatum surface adhesion-related proteins FadA and FomA. CONCLUSION: Our study demonstrated that proteases in P. gingivalis OMVs inhibited the invasion of F. nucleatum into oral epithelial cells by downregulating FadA and FomA.

miR-29a-3p promotes migration and invasion in ameloblastoma via Wnt/ß-catenin signaling by targeting catenin beta interacting protein 1.

BACKGROUND: Ameloblastoma (AB) is a common epithelial odontogenic tumor. The Wnt/ß-catenin pathway has been found to be related to AB invasion. METHODS: The alteration expression of microRNAs (miRNAs) and messenger RNAs (mRNAs) was performed by miRNA and mRNA microarray analysis and validated by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-29a-3p on migration and invasion in AB cells were evaluated by a transwell assay. Bioinformatic prediction was conducted using the miRSystem and validated by quantitative RT-PCR, western blot, and a luciferase reporter assay. RESULTS: miR-29a-3p was overexpressed in AB tissues, which promoted the migration and invasion of AB cells in vitro. Catenin beta interacting protein 1 (CTNNBIP1), a negative regulator of the Wnt/ß-catenin pathway, was predicted to be a target of miR-29a-3p. miR-29a-3p inhibited the expression of CTNNBIP1 and promoted the expression of the downstream molecules of the Wnt/ß-catenin pathway. CONCLUSIONS: miR-29a-3p promoted migration and invasion in AB via Wnt/ß-catenin signaling by targeting CTNNBIP1.

Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase.

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.

sRNA23392 packaged by Porphyromonas gingivalis outer membrane vesicles promotes oral squamous cell carcinomas migration and invasion by targeting desmocollin-2.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignant tumor. Periodontitis, a common chronic inflammatory disease, has been proven to increase the risk of oral cancers. Porphyromonas gingivalis (P. gingivalis), the major pathogen in periodontal disease, was recently shown to promote the development of OSCC. However, the underlying mechanisms have not been defined. Emerging evidence suggests that P. gingivalis outer membrane vesicles (OMVs) contain different packaged small RNAs (sRNAs) with the potential to target host mRNA function and/or stability. In this study, we found that P. gingivalis OMVs promote the invasion and migration of OSCC cells in vitro. Further research showed that sRNA23392 was abundant in P. gingivalis OMVs and it promoted the invasion and migration of OSCC cells by targeting desmocollin-2 (DSC2). DSC2, a desmosomal cadherin family member, has been found to be involved in tumor progression. sRNA23392 inhibitors attenuated P. gingivalis OMV-induced migration and invasion of OSCC cells. Collectively, these findings are consistent with the hypothesis that sRNA23392 in P. gingivalis OMVs is a novel mechanism of the host-pathogen interaction, whereby P. gingivalis promotes the invasion and migration of OSCC.

Roles of the HGF/Met signaling in head and neck squamous cell carcinoma: Focus on tumor immunity (Review).

c­mesenchymal­epithelial transition (Met) is a transmembrane tyrosine kinase receptor of hepatocyte growth factor (HGF). HGF/Met signaling stimulates numerous pathways, including the Ras/mitogenactivated protein kinase (MAPK), phosphatidylinositol 3­kinase/protein kinase B and Wnt/ß­catenin pathways, which serve important roles in cell proliferation, survival, motility, invasion and angiogenesis, and promotes the development and progression of tumors. Aberrant HGF/Met signaling is associated with a poor prognosis in several types of tumors, including head and neck squamous cell carcinoma (HNSCC). Although, the HGF/MET pathway and HGF and/or Met inhibitors have been extensively reviewed, their role in tumor immunity remains elusive. The present review article summarizes the findings on the HGF/Met signaling in HNSCC, including gene and protein alterations, biological functions and patient outcomes. Furthermore, the role of HGF/Met in tumor immunity is discussed and the controversial association between the expression of HGF/Met and the prognosis of patients with HNSCC from the perspective of tumor immunity is clarified. Ultimately, the present review proposes a clinical approach that may improve the efficacy of Met therapy for HNSCC, namely the intratumoral administration of Met inhibitors in order to reduce the inhibitory effect on immune cell recruitment. However, further studies are required to provide an improved understanding of the effects of the HGF/Met pathway on the tumor microenvironment, and the effects of HGF and Met inhibitors on immune cells in the tumor environment should be the focus of future studies.

RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma.

Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor-associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP-1 cells, promoted M2-like macrophage polarization in vitro, and increased the proportion of M2-like macrophages in a xenograft mouse model. Moreover, both M1- and M2-like macrophage polarization-associated proteins were induced in macrophages cocultured with RACK1-silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C-C motif chemokine 2 (CCL2), C-C motif chemokine 5 (CCL5), interleukin-6 (IL-6), and interleukin-1 (IL-1) are closely related to RACK1 expression. In addition, blocking nuclear factor-kappa B (NF-κB) could promote M2-like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2-like polarization by regulating NF-κB and could be used as a potential therapeutic target for antitumor immunity.

The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Related Systemic Diseases.

Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a variety of systemic system diseases such as cancer, cardiovascular disease, diabetes, rheumatoid arthritis, non-alcoholic fatty liver, and Alzheimer's disease. Porphyromonas gingivalis (P. gingivalis) is the most important pathogenic bacteria for periodontal disease. It can produce outer membrane vesicles (OMVs) and release them into the environment, playing an important role in its pathogenesis. This article focuses on P. gingivalis OMVs, reviews its production and regulation, virulence components, mode of action and related diseases, with a view to providing new ideas for the prevention and treatment of diseases related to P. gingivalis infections.

PA28γ acts as a dual regulator of IL-6 and CCL2 and contributes to tumor angiogenesis in oral squamous cell carcinoma.

PA28γ promotes tumor development and progression and is suggested to play a role in tumor angiogenesis, but the molecular mechanisms have not been investigated. Here, we found that PA28γ enhanced the ability of OSCC cells to promote the migration, invasion, and tube formation of HUVECs and promoted tumor-induced angiogenesis in xenograft mice models in vivo. Then, a mechanism study revealed that the expression and secretion of IL-6 and CCL2 were dependent on PA28γ expression. Furthermore, blocking IL-6 or CCL2 or the transcription factor NF-κB induced the inhibition of tube formation in HUVECs co-cultured with PA28γ-overexpression OSCC cell supernatants. Moreover, we revealed that p-STAT3 and p-AKT, which are downstream of the IL-6 and CCL2 signaling axis, were downregulated in HUVECs co-cultured with the PA28γ-silenced supernatant and were upregulated with the PA28γ-overexpressing supernatant. In addition, IL-6, CCL2 and PA28γ expressions were correlated in a clinical OSCC cohort. Collectively, our study indicates that PA28γ contributes to tumor angiogenesis by regulating IL-6 and CCL2. PA28γ may be a novel therapeutic target as a dual regulator of IL-6 and CCL2 for treating PA28γ-positive OSCC.

Analysis of clinicopathological characteristics associated with the outcome of oral squamous cell carcinoma and the establishment of tissue microarrays.

The aim of this study was to evaluate clinicopathological risk factors associated with the fatal outcome of oral squamous cell carcinoma (OSCC) in a large cohort of Chinese patients, and to construct tissue microarrays (TMAs) using this cohort. Univariate and multiple logistic regression analyses were performed to evaluate the predictors of poor prognosis in a cohort of 232 patients with OSCC, after which the patient tumor tissues were used to construct TMAs. Univariate logistic regression analysis indicated that a poor outcome of OSCC was associated with the male gender, a history of smoking, the tumor-node-metastasis stage and lymph node metastasis. Multiple logistic regression analysis demonstrated that an increased risk of mortality in patients with OSCC was significantly and independently associated with lymph node metastasis (odds ratio, 3.421; 95% confidence interval, 1.609-7.273). Therefore, the results of the present study suggested that lymph node metastasis is an independent risk factor associated with a poor prognosis of OSCC patients. TMAs of OSCC were successfully constructed, and are the first TMAs to be reported in mainland Chinese patients.

Interleukin-37 expression and its potential role in oral leukoplakia and oral squamous cell carcinoma.

Interleukin 37 (IL-37) has been reported to play a significant role in innate immune response and to be involved in several kinds of cancers. However, the investigation of association between IL-37 and oral mucosa carcinogenesis hasn't been clearly established. The aim of the study was to assess IL-37 expression and explore its role in oral mucosa carcinogenesis. The expression of IL-37 increased from normal control (NC) to Oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Moreover, statistically highly significant difference was present between scores of OLK with and without mild/moderate dysplasia (P < 0.001). In addition, IL-37 expression was lower in OSCC with lymph node metastasis than those without metastasis (P < 0.01). What's more, overexpression of IL-37 in RAW264.7 cells remarkably reduced the pseudopodia, vacuolization and the expression of IL-6, TNF-α, and IL-1ß. Finally, we found IL-37 and its receptor IL-18Rα but not its binding partner IL-18BP have similar tissue location and expression trend in different stages of oral mucosa carcinogenesis. Overall, IL-37 can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions.

Regulatory T cells in oral squamous cell carcinoma.

Regulatory T cells (Tregs) play a critical role in modulating and maintaining immune homeostasis and tolerance. They accumulate in many types of tumors and play a critical role in tumor evasion of immune surveillance. Oral cancer is characterized by an increase in the number of infiltrating Tregs; however, the significance of this increase on the prognosis of oral cancer is controversial. This review focuses on the function of Tregs in oral squamous cell carcinoma and its implications on prognosis. We also discuss potential therapeutic strategies aimed at Tregs modification in oral SCC.

Non-Invasive Techniques for Detection and Diagnosis of Oral Potentially Malignant Disorders.

Oral squamous cell carcinoma (OSCC) is the most common oral and maxillofacial malignancy, and its morbidity and mortality rates are still high in most countries. Oral potentially malignant disorders (PMDs) are used to refer to a heterogeneous group of conditions that are characterized by increased risk for malignant transformation to OSCC. Currently identified oral PMDs include leukoplakia, erythroplakia, palatal lesions associated with reverse smoking, oral lichen planus, oral submucous fibrosis, actinic keratosis, and discoid lupus erythematosus. The early detection and diagnosis of these lesions are important for cancer prevention and disease management. In recent years, there has been a growing and persistent demand for new non-invasive, practical diagnostic techniques that might facilitate the early detection of oral PMDs. The non-invasive detection techniques evaluated in this review are divided into four categories: vital staining with a solution that can be used as a mouth rinse or applied onto a suspected area of the mouth, light-based detection systems, optical diagnostic technologies that employ returned optical signals to reflect structural and morphological changes within tissues, and salivary biomarkers. Most of these techniques have shown great potential for screening and monitoring oral PMDs. In this review article, the authors critically assess these non-invasive detection techniques for oral PMDs. We also provide a summary of the sensitivity and specificity of each technique in detecting oral PMDs and oral cancer, as well as their advantages, disadvantages, clinical applications, and indications.

Single-prolonged stress induce different change in the cell organelle of the hippocampal cells: A study of ultrastructure.

MRI studies have revealed structural and functional changes in the hippocampus of post-traumatic stress disorder (PTSD) patients. Previous studies conducted by us in a PTSD animal model found that single prolonged stress (SPS) induced abnormal morphological changes in hippocampal cells. The effects of SPS on cellular organelles of the hippocampal neurons remain unknown; however, these changes have been involved in SPS-induced abnormal hippocampal function. The aim of the present study is to examine ultrastructural changes in cellular organelles, including the lysosomes, mitochondria (Mit), Golgi apparatus, and endoplasmic reticulum (ER), following SPS exposure using transmission electron microscopy, enzyme histochemistry, and enzyme cytochemistry. First, morphological changes of the hippocampal cells and ultrastructural changes in cellular organelles, including lysosomes, ER, and Mit-induced by SPS were observed. Results from histo- and cytochemistry demonstrated that the Mit marker enzyme, cytochrome c oxidase (COX), and the lysosomal enzyme acid phosphatase, (ACP), increased following exposure to SPS. SPS induced COX release from Mit and led to a wider distribution of ACP in round lysosomes, NLY, and the Golgi. In addition, we found that SPS increased the presence of autophagosomes and induced changes in the autophagy-related protein, Beclin. These results indicated the differential effects of SPS on cellular organelles, that is, a positive effect on lysosomes as well as a negative effect on the Mit and ER. Increased lysosomal function may serve as protection against SPS-induced cell damage. Structural changes in the Mit and ER may be involved in SPS-induced disorders of energy metabolism and protein synthesis and export.

RNAi-mediated downregulation of oral cancer overexpressed 1 (ORAOV1) inhibits vascular endothelial cell proliferation, migration, invasion, and tube formation.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the top ten tumors threatening human health. Oral cancer overexpressed 1 (ORAOV1) identified within chromosomal region 11q13, one of the most frequently amplified regions in OSCC, has been suggested as a novel candidate oncogene in OSCC, regulating cell cycle, apoptosis, and angiogenesis. In this study, we investigated the role of ORAOV1 in OSCC-induced angiogenesis in vitro. METHODS: EA.hy926 human endothelial cells were co-cultured with OSCC cells (HSC-3 and SCC-25) transfected with ORAOV1-specific shRNA to downregulate ORAOV1 expression, and analyzed for proliferation, migration, invasion, and tube formation by specific assays. RESULTS: EA.hy926 endothelial cells co-cultured with ORAOV1-deficient OSCC cells exhibited significantly lower proliferation, migration, and invasion, as well as the activity in tube formation compared to that in the control cells. CONCLUSIONS: Our results show, for the first time, that ORAOV1 expressed by OSCC cells promotes tube formation by endothelial cells, indicating its involvement in OSCC angiogenesis. Considering the importance of neovascularization in tumor development and metastasis, these findings suggest that targeting ORAOV1 may be a potential therapeutic strategy against OSCC.

Self-Assembling Monomeric Nucleoside Molecular Nanoparticles Loaded with 5-FU Enhancing Therapeutic Efficacy against Oral Cancer.

Conventional oligonucleotide based drug delivery systems suffer from lengthy synthetic protocols, high cost, and poor chemical or enzymatic stability under certain circumstances. Canonical free individual nucleosides cannot form stable nanostructures in aqueous solution as drug vehicles. Here, we report the development of a monomeric self-assembled nucleoside nanoparticle (SNNP) into an efficient drug delivery system which has currently no parallel in such field. This was achieved using a l-configurational pyrimido[4,5-d]pyrimidine nucleoside building block that can form robust discrete nanoparticles in just one step with water as the sole solvent. Its high biocompatibility and low toxicity was demonstrated in vitro and in vivo. In mouse xenograft model of oral squamous cell carcinoma (OSCC), SNNP loaded with 5-fluoro-uracile (5-FU-SNNP) remarkably retarded the tumor growth compared with free 5-FU, albeit SNNP alone showed no antitumor effect. The stability in blood circulation and the effective concentration of 5-FU in tumor tissue were increased upon the loading with SNNP. TUNEL and immunohistochemistry analyses further indicated that the superior in vivo antitumor efficacy of 5-FU-SNNP compared to free 5-FU was associated with an enhanced degree of inhibition of cell proliferation and stimulation of cell apoptosis. Furthermore, SNNP alleviated the toxic side effects of 5-FU. These findings suggested that when loaded with SNNP, 5-FU has better antitumor efficacy and lower side effects, indicating that SNNP can efficiently act as a readily accessible, robust, biocompatible and low-toxic nanobiomaterial which may find wide therapeutic applications clinically in the future.

A novel transcript variant of proteasome activator 28γ: Identification and function in oral cancer cells.

Proteasome activator 28γ (PA28γ) binds to and activates the proteasome in an ATP-independent manner to promote mainly ubiquitin-independent protein degradation in cells. Previously, four transcript variants of PA28γ have been identified, which have been closely correlated with the progression of cancers. In the present study, we predicted the alternative splicing of PA28γ via the bioinformatics tool ASPicDB and 49 splices were predicted. Then, we cloned some new segment according to predication in oral cancer cells using reverse transcription PCR and a novel variant of PA28γ was found. The novel transcript encodes a truncated form compared with other isoforms of PA28γ. However, it contains most of the conserved residues and the 'activation loop' of the PA28γ family. In order to explore its function, we overexpressed the variant in HEK293 cells and demonstrated that this variant is likely to further regulate cell cycle and apoptosis via regulating p53 and the mouse double minute2 homolog (Mdm2).