POLE2 Regulates Apoptosis of Oral Squamous Cell Carcinoma Cells through the PI3K/AKT Signaling Pathway

Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs.The second major subunit of DNA polymerase(POLE2)catalyzes the prolongation of new strand replication and modifies exonuclease domain activity.Our previous study found that POLE2 was associated with OSCC progression,but the mechanism remains unclear.Methods The expression of POLE2 in OSCC tissues was detected using immunological assays.Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC.POLE2 expression was inhibited in OSCC cells,and the effects of gene and protein expression were detected using RT-PCR and Western blotting.The POLE2 knockout model was constructed by transfecting a lentiviral vector.Cell proliferation,apoptosis,and migration were detected using various assays including colony formation,MTT,flow cytometry,wound healing assay,Transwell assay,and the Human Apoptosis Antibody Array.The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice.After 30 days,tumors were removed under anesthesia and tumor weight and dimension were recorded.Tumor cell proliferation was analyzed using Ki67 staining.Results POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues.In addition,POLE2 gene levels were statistically correlated with tumor classification and prognosis.Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro.Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation.We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3,CD40,CD40L,DR6,Fas,IGFBP-6,p21,and SMAC.In addition,POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway.Conclusion POLE2 is closely related to the progression of OSCC.Thus,POLE2 may be a potential target for OSCC treatment.

Effect of early nutrition on intestine development of intrauterine growth retardation in rats and its correlation to leptin

AIM: To investigate the intestine and body development of intrauterine growth retardation (IUGR) rats under early different protein diet and to analyze the correlation between leptin and intestine and body development.METHODS: An IUGR rat model was established by food restriction of pregnant female rats. Fifty-six neonatal IUGR rats and 24 neonatal normal rats were randomly divided into normal control group (C group), IUGR model group (SC group), low protein diet IUGR group (SL group), and high protein diet IUGR group (SH group). Eight rats were killed per group at wk 0, 4, and 12. Serum leptin, body weight (BW), body length (BL), intestinal weight (IW),intestinal length (IL), and intestinal disaccharidase (including lactase, maltase, and saccharase) were detected.RESULTS: BW (4.50±0.41 g), BL (5.96±0.40 cm), IW (0.05±0.01 g), and IL (15.9±2.8 cm) in neonatal IUGR rats were much lower than those in C group (6.01±0.55 g,6.26±0.44 cm, 0.10±0.02 g, 21.8±2.7 cm, P＜0.05), while intestinal lactase and maltase activities were higher than those in C group. SH group showed the fastest catch up growth and their BW, BL, IW, and IL reached the C group level at wk 4. SC group showed relatively slower catch up growth than SH group, and their BW, BL, IW did not reach the C group level at wk 4. SL group did not show intestine and body catch up growth. Intestinal maltase [344±33 μmol/(min.g)] and saccharase activities [138±32μmol/(min.g)] in SL group were both markedly lower than those in C group [751±102, 258±27 μmol/(min.g), P＜0.05].There were no significant differences in lactase activities at wk 4 and disaccharidase activities at wk 12 among all groups (P＞0.05). The leptin level in SL group (0.58±0.12ng/mL) was the highest in all groups, and much lower in SH group (0.21±0.03 ng/mL) than that in any other IUGR groups at wk 4 (P＜0.05). Leptin was negatively related to BW (r= -0.556, P = 0.001), IW (r= -0.692, P= 0.001)and IL (r = -0.738, P = 0.000) at wk 4, while no correlation was found at wk 12.CONCLUSION: High protein diet is a reasonable early nutritional mode to IUGR rats in promoting intestine and body catch up growth.

Conservative endodontic management using a calcium silicate bioceramic sealer for delayed root fracture:A case report and review of the literature

BACKGROUND The success rate of conservative endodontic management for root fracture varies greatly based on different methods used.It has been rarely reported that calcium silicate-based materials are applied in root fracture treatment.CASE SUMMARY A 38-year-old male patient presented with spontaneous pain from the upper left anterior teeth for 1 wk.The spontaneous pain was subsequently relieved,but pain on mastication persisted for 3 d.The patient had a dental trauma from a boxing match 15 years ago.Cone beam computed tomography showed that the maxillary left central incisor had oblique fracture lines and a radiolucent lesion around the fracture line.The tooth was diagnosed with an oblique root fracture with no healing and symptomatic apical periodontitis.In the following conservative endodontic management,the coronal and apical fragments of the canal both were chemo-mechanically prepared and obturated using a single cone gutta-percha with iRoot SP(Innovative BioCreamix Inc,Vancouver,Canada),a new calcium silicate-based bioceramic root canal sealer.At follow-ups at 1,6,12,and 24 mo,the patient was asymptomatic and the radiolucency around the fracture line was healing radiographically.CONCLUSION Conservative root canal treatment is an alternative treatment in some cases of oblique root fracture with no healing.The application of bioceramic sealers and single core obturation techniques may also be essential to obtain an excellent outcome.

A large basal cell adenoma extending to the ipsilateral skull base and mastoid in the right parotid gland: A case report

BACKGROUND Basal cell adenoma (BCA) is a rare benign tumour that has unique histological characteristics and primarily arises in the parotid glands. According to published reports, nearby tissue destruction by BCA seems impossible. CASE SUMMARY We presented a case of a 54-year-old woman with a mass in the deep lobe of the right parotid gland involving the ipsilateral skull base and mastoid. The patient exhibited gradual right facial swelling but no other obvious symptoms. Combined resection of the total right parotid gland and partial skull base excision were performed. The biopsy conducted before the surgery and sections cut from intraoperatively obtained tissues were not definitive for identifying the character of the neoplasm. A final diagnosis of tubular BCA without malignant elements was established based on postoperative pathology results and immunohistochemical analysis. The tumour did not recur during the 12-mo follow-up period. CONCLUSION A diagnosis of BCA can only be established based on a histopathological examination after an excisional biopsy, and tubular BCA should carefully be considered as a destructive type.

Evolution of Dislocation Loops in AL-6XN Stainless Steels Irradiated by Hydrogen Ions

AL-6XN stainless steels, one of the candidate structure materials for supercritical water-cooled reactor, were irradiated from 0.5 to 5 dpa using 100 keV H2＋ ions at 290 and 380 ℃. Microstructures were characterized by transmission electron microscopy （TEM）. Dislocation loops were the dominant radiation-induced defects. All the dislocation loops had 1/3 〈111〉 type Burgers vector. Number density and size of the loops have been measured. Nucleation and evolution of dislocation loops were also investigated. Voids were observed only in the condition of 5 dpa at 380 ℃. Different evolution mechanisms of the radiation-induced dislocation loops were discussed. Effects of hydrogen and elevated temperature on the microstructural evolution were also investigated. Besides, the formed voids have a further effect on the evolution of dislocation loops.