Yuehong Wang

Distal-less homeobox 2 promotes the osteogenic differentiation potential of stem cells from apical papilla.

Dental tissue-derived mesenchymal stem cells (MSCs) are a reliable cell source for dental tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. The histone demethylase, lysine (K)-specific demethylase 4B (KDM4B), plays critical roles in the osteogenic commitment of MSCs by up-regulating distal-less homeobox 2 (DLX2) expression. The DLX2 gene is highly expressed in dental tissue-derived MSCs but the roles of DLX2 in osteogenesis are unclear. Here, we investigate DLX2 function in stem cells from apical papilla (SCAPs). We found that, in vitro, DLX2 expression was up-regulated in SCAPs by adding BMP4 and by inducing osteogenesis. The knock-down of DLX2 in SCAPs decreased alkaline phosphatase (ALP) activity and mineralization. DLX2 depletion affected the mRNA expression of ALP, bone sialoprotein (BSP) and osteocalcin (OCN) and inhibited SCAP osteogenic differentiation in vitro. Over-expression of DLX2 enhanced ALP activity, mineralization and the expression of ALP, BSP and OCN in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when DLX2 was activated. Furthermore, DLX2 expression led to the expression of the key transcription factor, osterix (OSX) but not to the expression of runt-related transcription factor 2 (RUNX2). Taken together, these results indicate that DLX2 is stimulated by BMP signaling and enhances SCAP osteogenic differentiation by up-regulating OSX. Thus, the activation of DLX2 signaling might improve tissue regeneration mediated by MSCs of dental origin. These results provide insight into the mechanism underlying the directed differentiation of MSCs of dental origin.

An adaptive immune response driven by mature, antigen-experienced T and B cells within the microenvironment of oral squamous cell carcinoma.

Lymphocyte infiltrates have been observed in the microenvironment of oral cancer; however, little is known about whether the immune response of the lymphocyte infiltrate affects tumor biology. For a deeper understanding of the role of the infiltrating‐lymphocytes in oral squamous cell carcinoma (OSCC), we characterized the lymphocyte infiltrate repertoires and defined their features. Immunohistochemistry revealed considerable T and B cell infiltrates and lymphoid follicles with germinal center‐like structures within the tumor microenvironment. Flow cytometry demonstrated that populations of antigen‐experienced CD4+ and CD8+ cells were present, as well as an enrichment of regulatory T cells; and T cells expressing programmed death‐1 (PD‐1) and T cell Ig and mucin protein‐3 (Tim‐3), indicative of exhaustion, within the tumor microenvironment. Characterization of tumor‐infiltrating B cells revealed clear evidence of antigen exposure, in that the cardinal features of an antigen‐driven B cell response were present, including somatic mutation, clonal expansion, intraclonal variation and isotype switching. Collectively, our results point to an adaptive immune response occurring within the OSCC microenvironment, which may be sustained by the expression of specific antigens in the tumor.

CD147 and Prostate Cancer: A Systematic Review and Meta-Analysis.

Background Prostate cancer is one of the most common non-cutaneous malignancies in men. We aimed to systemically evaluate the relationship between the expression of CD147 in tissues and the clinicopathological features of prostate cancer. Methods and Findings PubMed (1966–2016), EMBASE (1980–2016), the Cochrane Library (1996–2016), Web of Science (1945–2016), China National Knowledge Infrastructure (1982–2016), and the WanFang databases (1988–2016) were searched. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis was performed by using Review Manager 5.3 and Stata 13.0. A total of 12591 prostate cancer patients from 14 studies were included. The results of the meta-analysis showed that there were significant differences in the positive expression rate in the following comparisons: prostatic cancer tissues vs. normal prostate tissues (odds ratio [OR] = 26.93, 95% confidence interval [CI] 7.95–91.20, P < 0.00001), prostatic cancer tissues vs. benign prostatic hyperplasia tissues (OR = 20.54, 95% CI 8.20–51.44, P < 0.00001), high Gleason score vs. low Gleason score (OR = 2.39, 95% CI 1.33–4.27, P = 0.03), TNM III to IV vs. TNM I to II (OR = 9.95, 95% CI 4.96–19.96, P < 0.00001), low or moderate differentiation vs. high differentiation (OR = 8.12, 95% CI 3.69–17.85, P < 0.00001), lymph node metastasis vs. non-lymph node metastasis (OR = 4.31, 95% CI 1.11–16.71, P = 0.03), and distant metastasis vs. non-distant metastasis (OR = 8.90, 95% CI 3.24–24.42, P < 0.00001). Conclusion The CD147 positive expression rate was closely related to the clinical characteristics of prostate cancer, but more research is needed to confirm the findings owing to the results of the subgroups.

Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma

It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels. It was also found that OSCC patients who suffered from disease stageⅠ-Ⅱ were more likely to have an up-regulated TPM1 expression level, and OSCC patients with lymph node metastasis had a higher probability of exhibiting reduced TPM1 expression. We show that overexpression of TPM1 can promote cell apoptosis and inhibit migration. Our results suggest that TPM1 can suppress tumors in OSCC, and the TPM1 expression level is related to OSCC patient prognosis.

Oral verrucous carcinoma: From multifactorial etiology to diverse treatment regimens (Review).

Oral verrucous carcinoma (OVC) is a verrucous variant of oral squamous cell carcinoma (OSCC), which accounts for 2-12% of all oral carcinomas with a 5-year survival rate of only approximately 50%. Enormous effort has been dedicated to this cancer, and the past decades have witnessed significant advances in relevant diagnostic and therapeutic approaches. Currently, there exist three challenges from primary sub-fields of research and clinical practice of the cancer, namely multifactorial etiology, complex molecular mechanism, and deficient treatment. This study reviews the existing literature on the cancer, encompassing its etiology, clinical manifestations and pathology, molecular mechanism, diagnosis and differential diagnosis, and treatment. For improved treatment of OVC, multifactorial etiology analysis, incorporation of effective biomarkers for mechanism illustration, and integration of multidisciplinary modalities are expounded, in an attempt to resolve the challenges and to provide a useful guide for future research in the field.

Electroactive BaTiO 3 nanoparticle-functionalized fibrous scaffolds enhance osteogenic differentiation of mesenchymal stem cells

It has been proven that the surface topographic cues of fiber arrangement can induce osteogenic differentiation of mesenchymal stem cells. However, this effect alone is weak and insufficient to meet the needs of regenerative medicine. In this work, electroactivity concept was introduced to enhance the osteoinductivity of fibrous scaffolds. The randomly oriented and aligned electroactive fibrous scaffolds of poly-(l-lactic acid) (PLLA) with incorporation of ferroelectric ceramic BaTiO3 (BTO) nanoparticles (NPs) were fabricated by electrospinning. Physicochemical properties, including fiber morphology, microstructure, composition, thermal stability, surface roughness, and surface wettability, of these fibrous scaffolds were studied. The dielectric properties of the scaffolds were evaluated. The results showed that the randomly oriented BTO/PLLA composite fibrous scaffolds had the highest dielectric permittivity of 1.19, which is of the same order of magnitude as the natural bone. The combined effects of fiber orientation and electrical activity on the osteogenic responses of bone marrow mesenchymal stem cells (BM-MSCs) were specifically investigated. Randomly oriented composite fibrous scaffolds significantly promoted polygonal spreading and encouraged early osteogenic differentiation in BM-MSCs, whereas aligned composite fibrous scaffolds promoted cell elongation and discouraged osteogenic differentiation. These results evidenced that randomly fiber orientation and biomimetic electric activity have combining effects on osteogenic differentiation of BM-MSCs. Our findings indicate that coupling effects of multi-physical properties should be paid more attention to mimic the microenvironment for enhancing osteogenic differentiation of BM-MSCs.

Proteomic analysis of human oral verrucous carcinoma

This study is about proteomic analysis of oral verrucous carcinoma (OVC). The total proteins obtained from tumour and adjacent normal oral mucosa of patients with OVC and oral squamous cell carcinoma (OSCC) were separated with two dimensional electrophoresis (2-DE) by using immobilized pH gradient strips and visualized by staining with silver nitrate. The gel images were acquired by scanner and 2-DE analysed by image master 2D elite. Twenty distinct protein spots were excised from gel randomly and digested in gel by TPCK-trypsin. Mass analysis of the tryptic digested peptides mixture was performed by using MALDI-TOF-MS. Peptide mass fingerprints (PMFs) obtained by the MALDI-TOF analysis were applied to National Center for Biotechnology Information (NCBI), SWISS-PROT and MSDB databases using Mascot software. Then the 2-DE gel imaging showed that 74, 36 and 31 differential protein spots were found between OVC and OSCC, OVC and adjacent normal oral mucosa of OVC (OVCN), OSCC and adjacent normal oral mucosa of OSCC (OSCCN) samples, respectively. By identification of protein spots from 2-DE gels, 20 PMF maps were obtained by MALDI-TOF-MS including recoverin (cancer associated retinopathy (CAR) protein) tumor protein D53 (hD53), zinc finger protein 77 (ZNFpT1) and so on and these protein may play a key role in the carcinogenesis of OVC and OSCC.