Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.

Interaction of cyclic naphthalene diimide derivatives (cNDIs), 1-4, with TA-core and c-myc as G-quartet (G4) DNA was studied under dilute or molecular crowding condition. Binding study for TA-core based on an isothermal titration calorimetry showed that 1-4 has 106 M-1 order of binding affinity with the following order: 1 > 4 > 2 > 3 under both conditions. Meting temperature (Tm) of TA-core obtained from the temperature dependence of circular dichroism spectra shows that TA-core was most stabilized by 4, which is in agreement with the result of PCR stop assay and the stabilization effect for 1-3 was correlated with their binding affinity under dilute condition. 3 showed specific growth inhibition of cancer cell line Ca9-22 at <0.03 µM of IC50, with no inhibitory effect against normal bone marrow cells. 3, which has highest value of ΔH/ΔG, shows the highest inhibition ability for Ca9-22, carrying a highest expression level of telomerase mRNA.

Msx1 Heterozygosity in Mice Enhances Susceptibility to Phenytoin-Induced Hypoxic Stress Causing Cleft Palate.

OBJECTIVE: Cleft palate is among the most frequent congenital defects in humans. While gene-environment multifactorial threshold models have been proposed to explain this cleft palate formation, only a few experimental models have verified this theory. This study aimed to clarify whether gene-environment interaction can cause cleft palate through a combination of specific genetic and environmental factors. METHODS: Msx1 heterozygosity in mice (Msx1+/-) was selected as a genetic factor since human MSX1 gene mutations may cause nonsyndromic cleft palate. As an environmental factor, hypoxic stress was induced in pregnant mice by administration of the antiepileptic drug phenytoin, a known arrhythmia inducer, during palatal development from embryonic day (E) 11 to E14. Embryos were dissected at E13 for histological analysis or at E17 for recording of the palatal state. RESULTS: Phenytoin administration downregulated cell proliferation in palatal processes in both wild-type and Msx1+/- embryos. Bone morphogenetic protein 4 (Bmp4) expression was slightly downregulated in the anterior palatal process of Msx1+/- embryos. Although Msx1+/- embryos do not show cleft palate under normal conditions, phenytoin administration induced a significantly higher incidence of cleft palate in Msx1+/- embryos compared to wild-type littermates. CONCLUSION: Our data suggest that cleft palate may occur because of the additive effects of Bmp4 downregulation as a result of Msx1 heterozygosity and decreased cell proliferation upon hypoxic stress. Human carriers of MSX1 mutations may have to take more precautions during pregnancy to avoid exposure to environmental risks.

Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan.

BACKGROUND: Therapeutic strategies for patients with medication-related osteonecrosis of the jaw (MRONJ) remain controversial. The aim of the present study was to clarify the effectiveness and safety of teriparatide therapy in Japanese MRONJ patients based on a large number of case series with a multicenter retrospective analysis. PATIENTS AND METHODS: Between January 2012 and December 2016, 29 patients who were diagnosed with MRONJ at 10 hospitals were treated with teriparatide. The medical records of these patients were retrospectively reviewed to assess the efficacy and safety of teriparatide therapy for MRONJ patients. RESULTS: Adverse events occurred in 17.2% of patients (5/29). One patient developed severe arthralgia and discontinued teriparatide therapy after 12 days, while others continued the treatment. Among 29 patients, the median period of administration of teriparatide was 14.0 months (range, 0.3-26 months), and treatment outcomes were evaluated as effective in 75.9% of patients with complete resolution in 65.5%. Among patients treated with oral bisphosphonates (BPs), 83.3% were effectively treated with teriparatide and 40% with intravenous BPs. The oral administration of BPs was associated with successful treatment outcomes with teriparatide (p = 0.062). CONCLUSIONS: Teriparatide therapy has potential as an effective treatment option for MRONJ.

Mechanisms involved in enhancement of osteoclast formation by activin-A.

Several growth factors in bone tissues are reported to be associated with osteoclastogenesis. Activin-A, a member of the transforming growth factor-ß (TGF-ß) family is known to be present in bone tissues and an important regulator in osteoclastogenesis with SMAD-mediated signaling being crucial for inducing osteoclast differentiation. In the present study, we examined the effect and underlying mechanisms of activin-A on osteoclast formation in vitro culture systems. Activin-A enhanced osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW 264.7 cells induced by receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) and/or macrophage stimulating factor (M-CSF). We also found that activin-A stimulated bone resorption and actin ring formation induced by RANKL and/or M-CSF. Furthermore, activin-A enhanced RANKL-induced expression of nuclear factor of activated T cell cytoplasmic 1 (NFATc1), a key regulator of osteoclastogenesis, thereby increasing osteoclastogenesis-related marker gene expression, including tartrate-resistant acid phosphatase, osteoclast stimulatory transmembrane protein, and cathepsin K. Blockage of receptor binding by follistatin, an activing-binding protein suppressed the activin-A-mediated stimulation of NFATc1. In addition, activin-A increased RANKL-induced c-fos expression without significantly affecting the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathway. Pre-treatment of the cells with a specific inhibitor of SMAD2/3 attenuated the activin-A-induced expression of NFATc1 and co-immunoprecipitation assay revealed that treatment with activin-A increased physical interaction of phosphorylated-c-fos and phosphorylated-SMAD2 protein induced by RANKL. These results suggest that activin-A enhances RANKL-induced osteoclast formation mediated by interaction of c-fos and smad2/3.

Ky-2, a hybrid compound histone deacetylase inhibitor, regulated inflammatory response in LPS-driven human macrophages.

Histone deacetylase has attracted much attention as an epigenetic factor, and the modulation of histone and transcription factor acetylation status is important for regulating gene expression. Moreover, histone deacetylase inhibitors are involved in cellular growth and differentiation. In the present study, we examined the effects of Ky-2, a hybrid-compound HDAC inhibitor, on inflammatory reactions and the polarization of macrophages in vitro. Human monocyte-like THP-1 cells were polarized to macrophage-like cells using phorbol 12-myristate 13-acetate, and then polarized to M1 macrophages with LPS. Ky-2 inhibited HDAC2 expression and enhanced the acetylation of histone H3 in THP-1 cells. It also downregulated the expression of the IL-1ß-encoding gene and the LPS-induced phosphorylation of p38 mitogen-activated protein kinases in THP-1 cells. Moreover, the expression of nod-like receptor protein 3 and cleaved caspase-1 p20 was downregulated in Ky-2-treated THP-1 cells. In contrast, this agent upregulated the expression of IL-1ra in LPS-treated THP-1 cells. These results indicate that Ky-2-treatment downregulates the expression of the inflammatory cytokine, IL-1ß, in LPS-treated THP-1 cells, suggesting that Ky-2 might regulate M1 macrophage polarization through the suppression of inflammatory responses such as NLRP3 inflammasome activation.

Comparison of the Effects of Ultrasonic and Conventional Surgery on the Neurosensory Disturbance After Bilateral Sagittal Split Osteotomy.

PURPOSE: According to the literature, ultrasonic surgery reduces the incidence of neurosensory disturbance (NSD) of the inferior alveolar nerve (IFAN) after bilateral sagittal split osteotomy (BSSO). The purpose of this study was to evaluate the effects of ultrasonic surgery and the anatomic position of the IFAN canal on NSD after BSSO. PATIENTS AND METHODS: This retrospective cohort study included skeletal mandibular prognathism cases operated on with an ultrasonic bone scalpel or a reciprocating saw. The primary predictor variable was osteotomy technique (ultrasonic or conventional surgery). The primary outcome variable was NSD. Other variables included age, gender, operator, degree of setback, surgical duration, blood loss, and IFAN position. Comparisons of 2 variables were performed by use of the Student t test or Fisher exact test. A regression model was used to examine the relationship between the presence or absence of NSD and other variables. The level of significance was set at P < .05 for all statistical tests. RESULTS: The ultrasonic group was composed of 35 patients, whereas the conventional group was composed of 32. Three months after surgery, NSD was observed on 16 of 70 sides (22.9%) in the ultrasonic group and 28 of 64 sides (43.8%) in the conventional group; this difference was significant. Furthermore, recovery from NSD at 3 months after BSSO was significantly more common in the ultrasonic group than in the conventional group. In the ultrasonic group, even when the distance from the buccal aspect of the IFAN canal to the outer buccal cortical margin was shorter, NSD of the IFAN was less frequent. CONCLUSIONS: Ultrasonic surgery may be an effective technique to reduce the incidence of NSD after BSSO, and it contributed to recovery from NSD. The use of an ultrasonic device for BSSO is recommended when the distance from the buccal aspect of the IFAN canal to the outer buccal cortical margin is shorter on computed tomography.

Lysophosphatidylethanolamine acyltransferase 1/membrane-bound O-acyltransferase 1 regulates morphology and function of P19C6 cell-derived neurons.

Glycerophospholipids, which are components of biomembranes, are formed de novo by the Kennedy pathway and subsequently mature through the Lands cycle. Lysophospholipid acyltransferases (LPLATs) are key enzymes in both pathways and influence the fatty acid composition of biomembranes. Neuronal differentiation is characterized by neurite outgrowth, which requires biomembrane biosynthesis. However, the role of LPLATs in neuronal differentiation remains unknown. In this study, we examined whether LPLATs are involved in neuronal differentiation using all-trans-retinoic acid (ATRA)-treated P19C6 cells. In these cells, mRNA levels of lysophosphatidylethanolamine acyltransferase (LPEAT)-1/membrane-bound O-acyltransferase (MBOAT)-1 were higher than those in undifferentiated cells. LPEAT enzymatic activity increased with 16:0- and 18:1-CoA as acyl donors. When LPEAT1/MBOAT1 was knocked down with small interfering RNA (siRNA), outgrowth of neurites and expression of neuronal markers decreased in ATRA-treated P19C6 cells. Voltage-dependent calcium channel activity was also suppressed in these cells transfected with LPEAT1/MBOAT1 siRNA. These results suggest that LPEAT1/MBOAT1 plays an important role in neurite outgrowth and function.-Tabe, S., Hikiji, H., Ariyoshi, W., Hashidate-Yoshida, T., Shindou, H., Okinaga, T., Shimizu, T., Tominaga, K., Nishihara, T. Lysophosphatidylethanolamine acyltransferase 1/membrane-bound O-acyltransferase 1 regulates morphology and function of P19C6 cell-derived neurons.

Modified Lateral Surgical Approach to the Pterygopalatine Fossa.

Oral cancer, especially that originates in the maxillary tuberosity, buccal mucosa, and maxillary alveolus, is apt to invade the pterygopalatine fossa, where an intraoral approach is nearly impossible. There are 2 main types of extraoral approach to the pterygopalatine fossa; the anterior approach and the lateral approach. Although the lateral approach has an advantage compared with the anterior approach in terms of cosmetics, after the operation numbness of the lower lip occurs due to the sacrifice of the mental nerve. In the conventional lateral approach, a vertical incision is made in the center of the lower lip; a lateral flap is then elevated with the sacrifice of the mental nerve. The authors introduce here a new lateral approach to the pterygopalatine fossa with preservation of the mental nerve. In the present technique, a vertical incision was made in the corner of the mouth, and a lateral flap was then elevated with preservation of the mental nerve. This technique could also preserve the marginal mandibular branch of facial nerve in patients without a large metastasis in the submandibular lymph nodes. Additionally, expedient mandibular osteotomy, which is applied in the conventional lateral approach, could be omitted in the present technique, thus helping to prevent postoperative infection. The present approach was applied to 5 patients with oral cancer invading the pterygopalatine fossa. The postoperative numbness of the lower lip was estimated using the current perception threshold. The lesions were successfully resected with little numbness of the lower lip, and no postoperative infection occurred in any of the patients. This technique is available as an approach to the pterygopalatine fossa that preserves the mental nerve and can prevent postoperative infection.

Essential Role of Lysophosphatidylcholine Acyltransferase 3 in the Induction of Macrophage Polarization in PMA-Treated U937 Cells.

Lysophospholipid acyltransferases (LPLATs) regulate the diversification of fatty acid composition in biological membranes. Lysophosphatidylcholine acyltransferases (LPCATs) are members of the LPLATs that play a role in inflammatory responses. M1 macrophages differentiate in response to lipopolysaccharide (LPS) and are pro-inflammatory, whereas M2 macrophages, which differentiate in response to interleukin-4 (IL-4), are anti-inflammatory and involved in homeostasis and wound healing. In the present study, we showed that LPCATs play an important role in M1/M2-macrophage polarization. LPS changed the shape of PMA-treated U937 cells from rounded to spindle shaped and upregulated the mRNA and protein expression of the M1 macrophage markers CXCL10, TNF-α, and IL-1ß. IL-4 had no effect on the shape of PMA-treated U937 cells and upregulated the M2 macrophage markers CD206, IL-1ra, and TGF-ß in PMA-treated U937 cells. These results suggest that LPS and IL-4 promote the differentiation of PMA-treated U937 cells into M1- and M2-polarized macrophages, respectively. LPS significantly downregulated the mRNA expression of LPCAT3, one of four LPCAT isoforms, and suppressed its enzymatic activity toward linoleoyl-CoA and arachidonoyl-CoA in PMA-treated U937 cells. LPCAT3 knockdown induced a spindle-shaped morphology typical of M1-polarized macrophages, and increased the secretion of CXCL10 and decreased the levels of CD206 in IL-4-activated U937 cells. This indicates that knockdown of LPCAT3 shifts the differentiation of PMA-treated U937 cells to M1-polarized macrophages. Our findings suggest that LPCAT3 plays an important role in M1/M2-macrophage polarization, providing novel potential therapeutic targets for the regulation of immune and inflammatory disorders.

IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression.

Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression.

Emergency Cricothyroidotomy for Difficult Airway Management After Asynchronous Bilateral Neck Dissections: A Case Report and Literature Review.

PURPOSE: This report describes a case that required emergency cricothyroidotomy for an upper airway obstruction owing to laryngeal edema after asynchronous bilateral neck dissections. PATIENT AND METHODS: A 57-year-old man was diagnosed with multicentric squamous cell carcinoma of the tongue (T1 and 2N0M0), and partial glossectomy with primary closure was performed. Three months after surgery, secondary metastases in the right cervical lymph nodes were detected, and a right radical neck dissection was performed. Contrast-enhanced computed tomographic (CT) scan taken 2 weeks after the right neck dissection visualized a possible third metastasis in the left cervical lymph node. Four weeks after the right radical neck dissection, left supraomohyoid neck dissection was carried out. In this surgery, the left internal jugular vein (IJV) was preserved. Nine hours after surgery, severe swelling of the face and pharynx was recognized, resulting in a stoppage of respiration and then an emergency cricothyroidotomy. RESULTS: The patient's life was saved without any encephalopathy or airway trouble. Contrast-enhanced CT scan taken the next day confirmed the preserved left IJV patency. CONCLUSION: Oral and maxillofacial surgeons should be aware of the possibility of life-threatening laryngeal edema associated with bilateral neck dissections even if the unilateral IJV is preserved and should know the procedure for emergency cricothyroidotomy.

Long-term follow-up after reimplantation of tumorous mandible bone treated with combination of decalcification and lyophilization.

Mandibular resection requires reconstruction, with often unsatisfactory morphofunctional results. Reimplantation of the resected mandible itself is one of ideal solutions to this problem. However, both devitalization of tumor cells involved in resected bone and preservation of osteoinductive activity are required for successful results. Lyophilization appears to enable devitalization of tumor cells, and decalcified bone implants are likely to have osteoinductive potential. Accordingly, we speculated that decalcification and lyophilization of resected bone would be an appropriate method for mandibular reconstruction. However, there is no study on the reimplantation of mandibles treated with these methods to date. The purpose of this study was to estimate the long-term follow-up of reimplanted mandibles treated with decalcification and lyophilization. Presented here are 2 patients of reimplanted mandibles treated by decalcification and lyophilization who were followed up for 8 and 9 years. We observed a good incorporation of the graft in 1 case, but severe absorption in the other. Our results suggest that treatment with decalcification and lyophilization is 1 strategy for reimplantation of the resected bone in mandibular reconstruction, but further study is needed to prevent absorption of the reimplanted bone over the long term.

Association between lymph node ratio and survival outcomes in patients with oral squamous cell carcinoma.

BACKGROUND: Recent reports have shown that the Lymph node ratio (LNR) is useful for predicting the prognosis in some cancers, however there are few reports on the usefulness of LNR in predicting the prognosis of oral squamous cell carcinoma (OSCC). The predictive value of LNR for prognosis of OSCC was investigated. MATERIALS AND METHODS: The study included 152 patients with OSCC and histologically confirmed cervical lymph node metastasis who underwent neck dissection. We analyzed the relationship between LNR and overall survival (OS) and recurrence-free survival (RFS) retrospectively in these cases, with the relationship between prognosis and clinicopathological findings also examined. RESULTS: Using a receiver operating characteristics curve, the LNR cutoff value was set at 0.095, categorizing 64 and 88 cases into high LNR (≥ 0.095) and low LNR (< 0.095) groups, respectively. Regarding OS and RFS, the prognosis was significantly worse in the high LNR group compared with the low LNR group. In multivariate analysis, sex, postoperative nodal stage, and LNR merged as independent prognostic factors. CONCLUSION: This study's findings suggest that LNR may represent a prognostic indicator in OSCC with cervical lymph node metastasis.

Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor.

OBJECTIVES: Histone deacetylase (HDAC) inhibitors are new therapeutic agents, used to treat various types of malignant cancers. In the present study, we investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth of mouse myeloma cells. MATERIALS AND METHODS: Myeloma cells, HS-72, P3U1, and mouse normal cells were used in this study. Effect of HDAC inhibitors on cell viability was determined by WST-assay and trypan blue assay. Cell cycle was analyzed using flow cytometer. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis. Hoechst's staining was used to detect apoptotic cells. RESULTS: Our findings showed that Ky-2 decreased the levels of HDACs, while it enhanced acetylation of histone H3. Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2 had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase cell cycle arrest and accumulation of a sub-G1 phase population, while Western blotting analysis revealed that expressions of the cell cycle-associated proteins were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to induce apoptosis in bcl-2 overexpressing myeloma cells. CONCLUSION: These findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and Bcl-2-inhibitable mechanism in myeloma cells.

Oral cancer diagnosis via a ferrocenylnaphthalene diimide-based electrochemical telomerase assay.

BACKGROUND: Telomerase is regarded as a good marker for cancer because it is unregulated in most tumor cells compared with normal cells. We evaluated telomerase activity in the lysate of tumor tissue and surrounding cells of oral cancer patients by an electrochemical technique, dubbed the electrochemical telomerase assay (ECTA). METHODS: The assay used ferrocenylnaphthalene diimide (FND) as the probe. Electrochemical telomerase substrate (ETS) primer immobilized on the electrode was elongated by telomerase and FND bound to the product to give rise to a current. The data were standardized with the change in current before and after the elongation, respectively. RESULTS: The change in current increased more than 30% in biopsy samples from most cancer patients, whereas the increase was 20% or lower in most healthy individuals. On the basis of this difference individual clinical samples were judged telomerase positive, ambiguous, or negative. The positive rates in the cancerous tissues and exfoliated cells (EOCs) of the patients were 85% and 90%, respectively, whereas the corresponding values were 50% and 10% by the telomerase repeat amplification protocol. Furthermore, the positive rate for the ECTA was 100% in early tumors smaller than 2 cm, and 95% and 82% of biopsy and exfoliated cells of healthy individuals were correctly judged as negative. Fifty-six unknown samples with EOCs tested were correctly judged to be cancerous or normal in 84% of cases. CONCLUSIONS: The ECTA yielded high hit rates for cancerous and normal cells, especially in EOCs, results indicating that this minimally invasive test is suitable for oral cancer diagnosis.

Surgical approach to the pterygopalatine fossa-comparison between anterior approach and lateral approach.

The anterior and the lateral approach for resecting an invading tumor in the pterygopalatine fossa region were compared. An anterior approach was applied for resecting a malignancy that originated from the maxillary tuberosity, upper hard plate, and maxillary sinus, and a lateral approach was applied for resecting a malignancy that originated from the upper gingiva and buccal mucosa. The anterior approach was capable of exposing the whole maxilla, although it was difficult to achieve such exposure by the lateral approach. However, the submandibular incision technique used in the Dingman approach was useful for upper neck dissection as well as for exposure of the artery and vein to anastomose them for reconstruction. The anterior approach should be useful for resection of the pterygopalatine fossa concomitant with total maxillectomy. On the other hand, the lateral approach might have an advantage in terms of its cosmetic effects.

Prevalence and imaging characteristics of detectable tonsilloliths on 482 pairs of consecutive CT and panoramic radiographs.

BACKGROUND: Recent studies suggest that tonsilloliths are clinically related to halitosis and tonsillar abscess. Based on our empirical knowledge, tonsilloliths are relatively commonly encountered in daily clinical practice. It has been reported that the detection rate of tonsilloliths was under 24% in previous reports, although experience suggests otherwise. The purpose of the study was to evaluate the prevalence and characteristics of tonsilloliths using computed tomography (CT). In addition, the possible causes of low detection rates on panoramic radiographs were evaluated based on comparisons between CT images and panoramic radiographs in order to elucidate the limitations of visualizing the area around the palatine tonsils on panoramic radiographs. METHODS: 482 pairs of CT images and panoramic radiographs were retrospectively assessed with respect to the presence and characteristics of tonsilloliths. In addition, the causes in cases of disagreement between the two modalities were analyzed. RESULTS: The detection rate of tonsilloliths was 46.1% using CT scans, unlike previous reports. The characteristics of tonsillolith were dot-like figures with about 300-500 Hounsfield units within the palatine tonsil under the soft palate. The most common length of tonsilloliths was about 3 or 4 mm. As the subjects aged, the detection rate increased gradually. A significant difference in the tonsillolith detection rate was found between the over and under 40-year-old groups (p < 0.0001). However, the detection rate of tonsilloliths was only 7.3% on panoramic radiographs. A significant correlation was observed between the detection rate of tonsilloliths on panoramic radiographs and CT number (Spearman r = 0.429), size, (Spearman r = 0.318), and number of tonsilloliths (Spearman r = 0.333). CONCLUSION: The present results suggest that tonsilloliths are relatively more common than previously suggested. However, panoramic radiographs detect only a small percentage of palatine tonsilloliths. The low detection rates on panoramic radiographs might be related to the degree of calcification, size, and number of tonsilloliths.

Post-reconstruction Free Flap Complications After Oral Cancer Ablation.

Introduction: Microvascular free flap transfer is considered a standard reconstruction after the ablation of oral cancer. Although the success rate is high, flap complications occasionally occur. This study investigated the reasons for and local factors involved in complications of free flap transfer and explored how to salvage the flaps. Patients and Methods: The cases of 53 patients who underwent a free flap transfer [radial forearm flaps (n = 36), abdominis musculocutaneous flaps (n = 6), scapular osteocutaneous flaps (n = 10), and fibular osteocutaneous flap (n = 1)] were analyzed: flap complications were observed in five of the cases. Results: In the all five cases, a salvage operation was performed under general anesthesia. The flap complications occurred within 33 h after anastomosis. In the salvage operation, thrombotic occlusion in veins of flap feeders was observed in three of the five cases. The possible reasons for flap complications were a twisting of the anastomosed vein where two veins were united, pressure to the feeder due to subcutaneous hematoma, and edema of adjacent tissue and/or drain tube; the reason was not clear in one case. The flaps were successfully salvaged in four cases by thrombectomy in veins, release of pressure at the veins, and/or interposition of the vein graft. Conclusion: Surgeons should pay close attention to the pressure and/or twisting in the feeder as well as the hemostasis in the surgical field, and a salvage operation should be carried out immediately when a flap complication is identified.

Horseshoe osteotomy maintains the nasal cavity and function after superior repositioning.

The aim of this prospective cohort study was to compare changes in nasal cavity and function between Le Fort I with and without horseshoe osteotomy after superior repositioning of the maxilla. The patients were divided into 2 groups, a Le Fort I alone (LF alone) group and a combination Le Fort I and horseshoe osteotomy (HS) group. The nasal cavity volume was measured using 3-dimensional computed tomographic images, and nasal resistance was assessed by anterior active mask rhinomanometry. The HS group consisted of 17 patients, and the LF alone group consisted of 15 patients. The magnitude of change in nasal cavity volume was significantly smaller in the HS group than in the LF alone group (p < 0.001), even though the mean amount of superior maxillary movement was considerably larger in the HS group than in the LF alone group (p < 0.001). Mean nasal resistance was significantly smaller postoperatively than preoperatively in the HS group (p < 0.05). Furthermore, the change in nasal resistance was smaller in the HS group than in the LF alone group (p < 0.001). Within the limitations of this study, it seems that horseshoe osteotomy is useful for maintaining the nasal cavity and function after superior repositioning of the maxilla.

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth.

Cyclic anthraquinone derivatives (cAQs), which link two side chains of 1,5-disubstituted anthraquinone as a threading DNA intercalator, have been developed as G-quartet (G4) DNA-specific ligands. Among the cAQs, cAQ-mBen linked through the 1,3-position of benzene had the strongest affinity for G4 recognition and stabilization in vitro and was confirmed to bind to the G4 structure in vivo, selectively inhibiting cancer cell proliferation in correlation with telomerase expression levels and triggering cell apoptosis. RNA-sequencing analysis further indicated that differentially expressed genes regulated by cAQ-mBen were profiled with more potential quadruplex-forming sequences. In the treatment of the tumor-bearing mouse model, cAQ-mBen could effectively reduce tumor tissue and had less adverse effects on healthy tissue. These results suggest that cAQ-mBen can be a potential cancer therapeutic agent as a G4 binder.