Expression of YT Domain Family Protein in Oral Squamous Cell Carcinoma and Its Correlation with the Prognosis.

Background: Proteins contained in the conserved YTH521-b homologous (YTH) domain, have m6A-dependent RNA binding activity. As an important part of YTH domain family proteins, YTHDF1 and YTHDF3 were shown to be associated with many cancers. This paper aimed to reveal the relationship between the expression of these two proteins and the clinical prognosis of OSCC, providing certain guidance for clinical treatment of OSCC. Methods: We detected the expression of YTHDF1 and YTHDF3 in 120 OSCC patients by immunohistochemical analysis. Statistical analysis was used to determine whether the high or low expression of these two genes was significantly associated with age, gender, histological type, clinical stage, or lymph node metastasis. The correlation curve and survival curve of the two genes were produced to evaluate the potential clinical significance. Results: We find the expression of YTHDF1 and YTHDF3 was increased in OSCC tissues compared to adjacent normal tissues. The statistical analysis showed that the expression of YTHDF1 and YTHDF3 was significantly associated with the clinical stage and histological type in OSCC patients. There was also a significant correlation between the expression of YTHDF1 and YTHDF3. A high expression of YTHDF1 and YTHDF3 was related to poor patient prognosis. Conclusion: Our findings suggest that a high expression of YTHDF1 and YTHDF3 may be related to poor patient prognosis.

Upregulation of mmu_circ_0001066 attenuates the inhibitory effect of bisphosphonates on osteoclastogenesis.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is the main adverse side effect of bisphosphonates (BPs), mainly owing to the inhibitory effect of BPs on osteoclastogenesis. CircRNAs were identified to be an important factor in regulating cellular processes. The aim of this study was to explore the effect of mmu_circ_0001066 on BP-inhibited osteoclastogenesis. MATERIALS AND METHODS: The expression of MRONJ-related miRNA in RANKL-induced RAW264.7 cells treated with BP was analyzed using qRT-PCR analysis. Bioinformatics techniques were applied to screen potential circRNAs. Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were used to examine the effect of mmu_circ_0001066 on osteoclastogenesis. Bioinformatics analysis, luciferase reporter assays, and Western blotting assays were performed to investigate the underlying mechanism. RESULTS: Four MRONJ-related miRNAs were upregulated in BP-treated RAW264.7 cells, and the expression of mmu_circ_0001066 was negatively correlated with those of MRONJ-related miRNAs. Furthermore, the upregulation of mmu_circ_0001066 partially attenuated the inhibitory effect of BP on osteoclastogenesis in RAW264.7 cells. Mechanistically, upregulated miR-16 suppressed osteoclastogenesis and miR-16 inhibitor increased osteoclastogenesis. Furthermore, we have identified that miR-16 is a downstream effector of mmu_circ_0001066. CONCLUSION: Our results suggest that mmu_circ_0001066 played an important role in the BP-mediated suppression of osteoclastogenesis, which lays a foundation for identifying mmu_circ_0001066 as a potential biomarker for MRONJ.

Upregulation of XRN2 acts as an oncogene in oral squamous cell carcinoma and correlates with poor prognosis.

BACKGROUD: The 5'-3' exoribonuclease 2 (XRN2) has been reported involved in several tumors. However, the clinical significance and molecular mechanism of XRN2 in oral squamous cell carcinoma (OSCC) have not been elucidated. MATERIALS AND METHODS: Immunohistochemistry (IHC) was used to investigate the expression of XRN2 in OSCC and adjacent noncancerous tissues, which was further identified by western blot and GEPIA2 database analysis. Moreover, the relationship between XRN2 expression and the clinicopathological characteristics and prognosis of OSCC patients was evaluated. In addition, in vitro, the effects of XRN2 on OSCC cells were evaluated by Cell Counting Kit-8 (CCK8) assay, colony formation assay, apoptosis assay, wound healing assay, and transwell assays. RESULTS: XRN2 was overexpressed in 44 of 77 (57.1 %) OSCC tissues. High expression of XRN2 was significantly associated with tumor differentiation (P=0.003), pathological clinical stage (P=0.045), lymph node metastasis (P=0.041), and poor overall survival (P=0.0013). Furthermore, the multivariate analysis suggested that XRN2 expression(P=0.002) was determined as an independent prognostic factor for patients with OSCC. Additionally, with functional assays in vitro, we found that downregulation of XRN2 inhibited cell proliferation, migration, and invasion, while promoted apoptosis of OSCC cells. Furthermore, knockdown of XRN2 in OSCC cells could increase the expression of E-cadherin but reduce the expression of Vimentin, which changes the characteristic of epithelial-mesenchymal transition (EMT). CONCLUSION: XRN2 is significantly overexpressed in OSCC tissues and its upregulation was closely associated with poor prognosis of OSCC patients. XRN2 could be a useful prognostic biomarker and a potential therapeutic target for OSCC.

CHNQD-00603 Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by the miR-452-3p-Mediated Autophagy Pathway.

Background: Periodontitis is a chronic and progressive disease accompanied by bone loss. It is still a challenge to restore the bone structure. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a decisive role in bone restoration and regeneration. Marine natural products (MNPs) have multiple biological activities, including anti-tumor and anti-inflammatory properties. However, the exploration of MNPs in osteogenesis is far from sufficient. Methods: We obtained a series of derivatives through structural optimization from 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloid isolated from Scopulariopsis sp. Some preliminary cytological experiments showed that CHNQD-00603, obtained by adding a methoxy group to the position C3 and a hydroxyl group to the position C4 of 4-phenyl-3,4-dihydroquinolin-2(1H)-one, might promote the osteogenic differentiation of BMSCs. To further investigate the effects of CHNQD-00603 on BMSCs, we performed a CCK-8 assay and qRT-PCR, alkaline phosphatase staining (ALP), and alizarin red S staining to assess the cytotoxicity and the ability of osteogenic differentiation of CHNQD-00603. The autophagy level was assessed and validated by WB, qRT-PCR, and transmission electron microscopy. Then, 3-methyladenine (3-MA) was added to further examine the role of autophagy. Based on the expression of autophagy-related genes, we predicted and examined the potential miRNAs by bioinformatics. Results: CCK-8 assay showed that CHNQD-00603 at 1 µg/ml did not influence BMSCs activity. However, the proliferation rate decreased from the seventh day. qRT-PCR, ALP staining, ALP activity assay, and Alizarin red S staining showed that the best concentration of CHNQD-00603 to promote osteogenic differentiation was 1 µg/ml. Further investigations indicated that CHNQD-00603 activated autophagy, and the inhibition of autophagy by 3-MA attenuated CHNQD-00603-enhanced osteogenic differentiation. Subsequently, the findings from bioinformatics and qRT-PCR indicated that miR-452-3p might be a regulator of autophagy and osteogenesis. Furthermore, we transfected BMSCs with miR-452-3p NC and mimics separately to further determine the function of miR-452-3p. The data showed that the overexpression of miR-452-3p moderated the level of autophagy and osteogenic differentiation of CHNQD-00603-treated BMSCs. Conclusion: Our data suggested that CHNQD-00603 promoted the osteogenic differentiation of BMSCs by enhancing autophagy. Meanwhile, miR-452-3p played a regulatory role in this process.

Sebaceous lymphadenocarcinoma of the parotid gland: A case report.

BACKGROUND: Sebaceous lymphadenoma is a benign tumor that occurs rarely in the salivary glands, most commonly in the parotid glands or periparotid lymph nodes, and even more rarely undergoes malignant transformation into a sebaceous lymphadenocarcinoma. CASE SUMMARY: We report an 82-year-old woman who presented with a painless mass in the right parotid region. We performed extended surgical resection of the parotid gland mass. Intraoperative pathology revealed a sebaceous lymphadenocarcinoma with metastasis into the periparotid cervical lymph nodes, so we also performed neck dissection and lymph node resection. Postoperative pathology confirmed the diagnosis. The literature review revealed that this was the seventh reported case of sebaceous lymphadenocarcinoma and the second reported case of cervical lymph node metastasis and infiltration of the skin of the parotid gland. CONCLUSION: Treatment of sebaceous lymphadenocarcinoma depends on the typing and clinical staging of the cancer. Extensive resection is the first choice, and adjuvant radiotherapy should be given to patients with high-grade tumors or those at an advanced clinical stage.

[Effects of MTA, iRoot SP and AH Plus on proliferation and differentiation of human periodontal ligament stem cells].

PURPOSE: To explore the effects of MTA, iRoot SP and AH Plus on periodontal ligament stem cells. METHODS: The periodontal ligament stem cells were cloned by limiting dilution culture method. The effects of MTA, iRoot SP and AH Plus on proliferation and apoptosis of periodontal ligament stem cells were detected by MTT and Annexin-V-FITC/PI double staining. Alizarin and qRT-PCR were used to evaluate the effect of MTA, iRoot SP and AH plus on osteogenesis of periodontal ligament stem cells. SPSS 21.0 software package was used for statistical analysis. RESULTS: MTA showed mild toxicity at 24 and 48 hours, AH Plus showed mild toxicity at 24 h. iRoot SP was the least (P<0.05) compared to MTA and AH Plus. The effect of three kinds of materials on apoptosis of periodontal ligament stem cells gradually decreased with the prolongation of time. Compared with the control group, the three kinds of materials were toxic at 3 d, the toxicity of MTA was the strongest and the toxicity of iRoot SP was the lowest(P<0.05). Mineralization nodules in MTA and iRoot SP group were significantly higher than those in AH Plus and control group. The expression of OC, RUNX2, COL1A and ALP gene was higher at 7, 14, 21 d than in the control group and the expression of iRoot SP mineralization was the greatest(P<0.05). CONCLUSIONS: The hardened iRoot SP is non-toxic to human periodontal ligament stem cells. Osteogenic ability and mineralization capacity of hardened iRoot SP on human periodontal ligament stem cells are better than MTA.

CircCDR1as upregulates autophagy under hypoxia to promote tumor cell survival via AKT/ERK½/mTOR signaling pathways in oral squamous cell carcinomas.

Autophagy, as an important non-selective degradation mechanism, could promote tumor initiation and progression by maintaining cellular homeostasis and the cell metabolism as well as cell viability. CircCDR1as has been shown to function as an oncogene in cancer progression, however, it remains largely unknown as to how autophagy is regulated by circCDR1as in oral squamous cell carcinoma (OSCC). In this study, we validated the functional roles of circCDR1as in regulation of autophagy in OSCC cells and further investigated how circCDR1as contributed to cell survival via up-regulating autophagy under a hypoxic microenvironment by using combination of human tissue model, in vitro cell experiments and in vivo mice model. We found that hypoxia promoted the expression level of circCDR1as in OSCC cells and elevated autophagy. In addition, circCDR1as further increased hypoxia-mediated autophagy by targeting multiple key regulators of autophagy. We revealed that circCDR1as enhanced autophagy in OSCC cells via inhibition of rapamycin (mTOR) activity and upregulation of AKT and ERK½ pathways. Overexpression of circCDR1as enhanced OSCC cells viability, endoplasmic reticulum (ER) stress, and inhibited cell apoptosis under a hypoxic microenvironment. Moreover, circCDR1as promoted autophagy in OSCC cells by sponging miR-671-5p. Collectively, these results revealed that high expression of circCDR1as enhanced the viability of OSCC cells under a hypoxic microenvironment by promoting autophagy, suggesting a novel treatment strategy involving circCDR1as and the inhibition of autophagy in OSCC cells.

[Optimal design by customized plate on reconstruction of maxillary unilateral defect via free fibula flap].

PURPOSE: To optimize reconstruction of maxillary unilateral defect by free fibula flap rapidly through 3D printing technique. METHODS: 3D models of reconstruction of unilateral maxillary defect by free fibula flap was established via CAD/CAM, metal customized plates and resin osteotomy guides were designed and manufactured via 3D printing technique, simulating operation was performed on models in vitro, and reconstructive accuracy after surgical simulation was analyzed using SPSS 18.0 software package. RESULTS: Digital models involving reconstructive bone and affiliated devices (plates and guides) were established and fabricated rapidly. There was no significant difference between simulating point on computer and surgical simulating point in vitro. CONCLUSIONS: The optimized design and customized plate can increase the accuracy of reconstruction of maxillary defects with free fibula in vitro, which is helpful for accurate surgical reconstruction.

[Comparative study of functional neck dissection and radical neck dissection for early oral squamous cell carcinoma].

PURPOSE: To evaluate the clinical effects of functional neck dissection(FND) and radical neck dissection(RND) on early oral squamous cell carcinoma (OSCC). METHODS: A total of 63 OSCC patients were divides into 2 groups. Patients in FND group (n=30) underwent functional neck dissection with preservation of sternocleidomastoid muscle, accessory nerve, internal jugular vein and great auricular nerve, while patients in RND group (n=33) underwent radical neck dissection. The follow-up data included movement of shoulder joint, great auricular nerve function, neck shape and local recurrent rate. SPSS 18.0 software package was used for data. RESULTS: There was no significant difference in age, gender, tumor location, T stage, N stage, histologic grades, pathological type, preoperative chemotherapy and postoperative chemotherapy between the two groups(P>0.05). Cervical lymph nodes was not palpable(N0) or the diameter was less than or equal to 3cm(N1) for all patients. Compared to RND, the activities of shoulder joint point, earlobe numbness and neck concave deformity were significantly improved with FND(P<0.05). Patients were followed up for 2 years, no significant difference was observed for neck recurrence between the two groups(P=1.000). CONCLUSIONS: FND can be safely performed in cN0 or cN1 OSCC patients, which avoids major complications with RND, and improves postoperative quality of life for OSCC patients with NO or N1 stage.

Quality of Life in Patients After Maxillectomy and Placement of Prosthetic Obturator.

PURPOSE: The aim of this study was to assess quality of life (QoL) and obturator functioning in patients having undergone a maxillectomy as a tumor ablative resection and rehabilitation with a prosthetic obturator. MATERIALS AND METHODS: The University of Washington Quality of Life scale version 4 (UW-QoLv4) and the Obturator Functioning Scale (OFS) were used to evaluate the self-reported QoL and obturator functioning. The effects of demographic and treatment variables on QoL were assessed using age, defect size, postoperative radiotherapy (RT), neck dissection, and dentition. RESULTS: The study included 16 men and 13 women with a mean age of 48.8 years. Of the 29 patients, 16 had a Brown Class 2a or smaller defect and 13 had a Brown Class 2b or larger defect. The mean OFS score (P = .004) and the physical (P = .001) and social-emotional function scores (P = .001) of the patients who received postoperative RT were significantly lower than those who did not receive postoperative RT. The subscales for swallowing (P = .008), saliva (P = .001), pain (P = .001), and shoulder function (P = .002) correlated strongly with postoperative RT on the UW-QoL. The subscales for pronunciation (P = .007) and saliva (P = .002) correlated significantly with RT on the OFS. The mean OFS scores were significantly lower for the patients with a Brown Class 2a or smaller defect than for Brown Class 2b or larger (P = .005). CONCLUSION: Postoperative RT was the strongest variable affecting QoL in patients with maxillectomy and prosthetic obturator reconstruction. The size of the defect slightly influenced the obturator function; however, it did not influence the overall QoL.

[A Study of the Relationship Among Genetic Distances, NIR Spectra Distances, and NIR-Based Identification Model Performance of the Seeds of Maize Iinbred Lines].

This paper explored the relationship among genetic distances, NIR spectra distances and NIR-based identification model performance of the seeds of maize inbred lines. Using 3 groups (total 15 pairs) of maize inbred lines whose genetic distaches are different as experimental materials, we calculates the genetic distance between these seeds with SSR markers and uses Euclidean distance between distributed center points of maize NIR spectrum in the PCA space as the distances of NIR spectrum. BPR method is used to build identification model of inbred lines and the identification accuracy is used as a measure of model identification performance. The results showed that, the correlation of genetic distance and spectra distancesis 0.9868, and it has a correlation of 0.9110 with the identification accuracy, which is highly correlated. This means near-Infrared spectrum of seedscan reflect genetic relationship of maize inbred lines. The smaller the genetic distance, the smaller the distance of spectrum, the poorer ability of model to identify. In practical application, near infrared spectrum analysis technology has the potential to be used to analyze maize inbred genetic relations, contributing much to genetic breeding, identification of species, purity sorting and so on. What's more, when creating a NIR-based identification model, the impact of the maize inbred lines which have closer genetic relationship should be fully considered.

Circulating microRNA-21 (MIR-21) and phosphatase and tensin homolog (PTEN) are promising novel biomarkers for detection of oral squamous cell carcinoma.

The purpose of this study was to investigate the potential of the blood levels of MIR-21 and PTEN as novel biomarkers for oral squamous cell carcinoma (OSCC). We initially detected MIR-21 and PTEN using real-time RT-PCR from 90 blood samples and then compared their results with expression in cancer tissues from 10 OSCC patients. Finally, we examined the relationship between these markers and clinical parameters. Blood MIR-21 and PTEN had significant diagnostic value for OSCC and, to an extent, correlated with the expression level of tumour MIR-21 and PTEN. In addition, they were associated with differentiation and nodal status. Thus circulating MIR-21 and PTEN might represent new complementary tumour markers for OSCC.

[Near infrared spectroscopy analysis method of maize hybrid seed purity discrimination].

Near infrared spectroscopy analysis method of discrimination of maize hybrid seed purity was studied with the sample of Nong Hua 101 (NH101) from different origins and years. Spectral acquisition time lasted for 10 months. Using Fourier transform (FT) near infrared spectroscopy instruments, including 23 days in different seasons (divided into five time periods), a total of 920 near infrared diffuse reflectance spectra of single corn grain of those samples were collected. Moving window average, first derivative and vector normalization were used to pretreat all original spectra, principal component analysis (PCA) and linear discriminant analysis (LDA) were applied to reduce data dimensionality, and the discrimination model was established based on biomimetic pattern recognition (BPR) method. Spectral distortion was calibrated by spectra pretreatment, which makes characteristics spatial distribution range of sample spectra set contract. The relative distance between hybrid and female parent increased by nearly 70-fold, and the discrimination model achieved the identification of hybrid and female parent seeds. Through the choice of representative samples, the model's response capacity to the changes in spectral acquisition time, place and environment, etc. was improved. Besides, the model's response capacity to the changes in time and site of seed production was also improved, and the robustness of the model was enhanced. The average correct acceptance rate (CAR) of the test set reached more than 95% while the average correct rejection rate (CRR) of the test set also reached 85%.

Protein overexpression of CIRP and TLR4 in oral squamous cell carcinoma: an immunohistochemical and clinical correlation analysis.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. Here, we evaluated the expression of cold-inducible RNA-binding protein (CIRP) and toll-like receptors 4 (TLR4) in OSCC tissues with immunohistochemistry. Using biostatistical methods designed to assess the impact of the expression of CIRP and TLR4 on the prognosis of patients with OSCC and relate that expression to the clinicopathological characteristics of these patients. For the first time, we demonstrated that the expression of CIRP and TLR4 was increased in OSCC and that high levels of CIRP or TLR4 expression were associated with a short survival rate. In addition, we were surprised to find that the levels of expression of CIRP and TLR4 were very similar. The goal of this study was to evaluate whether these two genes may provide clues as to the regulatory mechanisms of OSCC, serve as prognostic markers and establish a new direction for further studies of these biological mechanisms.

Organocatalytic synthesis of substituted spirocyclohexane carbaldehydes via [4 + 2] annulation strategy between 2-arylideneindane-1,3-diones and glutaraldehyde.

An organocatalytic domino reaction between 2-arylideneindane-1,3-diones and glutaraldehyde has been devised that gives functionalized spirocyclohexane carbaldehydes with an all-carbon quaternary center. The reaction proceeds through a Michael/Aldol sequence in good-to-high chemical yields and with high levels of stereoselectivity (up to >95:5 dr and 99% ee) in the presence of the α,α-L-diphenylprolinol trimethylsilyl ether 3 (20 mol %) and DIPEA (20 mol %) in ether at 0 °C.

Decompression as a treatment for odontogenic cystic lesions of the jaw.

PURPOSE: To evaluate the effectiveness of decompression as the primary treatment of odontogenic cystic lesions of the jaw involving factors that affect relative shrinking speed and bone regeneration. PATIENTS AND METHODS: A total of 32 patients with odontogenic cystic lesions of the jaw underwent decompression with customized thermoplastic resin stents. Clinical examinations and pre- and postdecompression panoramic radiographs were analyzed. RESULTS: The mean relative speed of shrinkage of radicular cysts (RCs; 3.37 cm(2)/month) was faster than those of keratocystic odontogenic tumors (KCOTs; 2.87 cm(2)/month) and unicystic ameloblastomas (UABs; 2.71 cm(2)/month). The relative shrinking size increased linearly in a time-dependent manner for KCOTs (r = 0.849, P < .001), RCs (r = 0.681, P = .319), and UABs (r = 0.146, P = .730); a similar relation was detected between the primary radiolucent area of cystic lesions before decompression and relative shrinking speed after decompression in KCOTs (r = 0.481, P = .032), RCs (r = 0.260, P = .673), and UABs (r = 0.370, P = .366), but patient age did not affect the relative speed of shrinkage (P > .05). Furthermore, the increase in bone density was more significant in RCs than in KCOTs (P = .026) and UABs (P = .012) after decompression. CONCLUSION: Decompression was effective in reducing odontogenic cystic lesions of the jaw and increasing bone density. For aggressive lesions, secondary definitive surgery was necessary.

[Feasibility study on an approach for identifying corn kernel varieties with seed coating agents via near infrared spectroscopy].

It is generally accepted that near infrared reflectance spectroscopy (NIRS) can be used to identify variety authenticity of bare maize seeds. In practical, maize seeds are covered with seed coating agents. Therefore it's of huge significance to investigate the feasibility of identifying coated maize seeds by NIRS. This study employed NIRS to quickly determine the variety of coated maize seeds. Influence of seed coating agent on NIR spectra was discussed. The NIR spectra of coated maize seeds were obtained using an innovative method to avoid the impact of the seed coating agent. Coated seeds were cut open, and the sections were scanned by the spectrometer, so as to acquire the information of the seed itself. Then, support vector machine (SVM), soft independent modeling of class analogy (SIMCA), and biomimetic pattern recognition (BPR) was employed to establish the identification model for four maize varieties, and yield 93%, 95.8%, 98% average correct rate respectively. BPR model showed better performance than SVM and SIMCA models. The robustness of identification model was tested by seeds harvested from four regions and model showed good performance.

[Study on method of maize hybrid purity identification based on hyperspectral image technology].

The feasibility of employing hyperspectral image technology to identify maize hybrid purity was studied by analyzing the spectral information of maize hyperspectral image. The hyperspectral images of hybrid and female parent of maize variety NH101 in the range of 871-1 699 nm including 308 wavelengths were collected by hyperspectral imaging system. We extracted average spectral information of interested region on maize seed and built identification models of hybrid and female parent of maize variety NH101 based on processed spectral data. The influences of different sample laying modes (seed embryo facing the light source, seed embryo backward light source, and seed put in different locations on sample stage) and experimental environments on the performance of identification models were discussed. Spectral collected under different sample laying modes and experimental environments were used to test the robustness of identification models. The average correct acceptance rates and average correct rejection rates are more than 90%. The feature spectral bands (1 195-1 246 nm) with which the differences between hybrid and female parent are the largest were extracted by a wavelength selection method based on standard deviations, called Qs. The performance of identification models built based on spectral data in feature spectral bands reached the same level of models built based on spectral data in the full range of 925-1 597 nm. The results demonstrated the feasibility of using hyperspectral image technology as an objective and rapid method for the identification of maize hybrid purity.