Differential Diagnosis of OKC and SBC on Panoramic Radiographs: Leveraging Deep Learning Algorithms.

This study aims to determine whether it can distinguish odontogenic keratocyst (OKC) and simple bone cyst (SBC) based solely on preoperative panoramic radiographs through a deep learning algorithm. (1) Methods: We conducted a retrospective analysis of patient data from January 2018 to December 2022 at Pusan National University Dental Hospital. This study included 63 cases of OKC confirmed by histological examination after surgical excision and 125 cases of SBC that underwent surgical curettage. All panoramic radiographs were obtained utilizing the Proline XC system (Planmeca Co., Helsinki, Finland), which already had diagnostic data on them. The panoramic images were cut into 299 × 299 cropped sizes and divided into 80% training and 20% validation data sets for 5-fold cross-validation. Inception-ResNet-V2 system was adopted to train for OKC and SBC discrimination. (2) Results: The classification network for diagnostic performance evaluation achieved 0.829 accuracy, 0.800 precision, 0.615 recall, and a 0.695 F1 score. (4) Conclusions: The deep learning algorithm demonstrated notable accuracy in distinguishing OKC from SBC, facilitated by CAM visualization. This progress is expected to become an essential resource for clinicians, improving diagnostic and treatment outcomes.

Characteristics of impacted mandibular third molar-related lesions.

Objectives: This study identifies factors for differential diagnosis among lesions by retrospectively comparing panoramic and cone-beam computed tomography images and analyzing the characteristics of lesions associated with impacted mandibular third molars (IMTs). Materials and Methods: A retrospective cohort study was conducted in patients who simultaneously underwent IMT extraction surgery and related benign tumor resection or cyst enucleation at our institution from 2017 to 2021. To compare the characteristics of each group, two comparative analyses were conducted. The first comparison considered the most frequently observed lesions associated with IMTs: dentigerous cysts, odontogenic keratocysts (OKCs), and ameloblastoma. The second comparison involved placing dentigerous cysts, which have a relatively low recurrence rate, into group A and placing OKC, ameloblastoma, and odontogenic myxoma, which have high recurrence rates, into group B. Results: Significant differences in the size of the lesion were found in the order of ameloblastoma, OKC, and dentigerous cyst (P <0.05). The buccolingual width of ameloblastoma differed significantly from that of the other groups, with no significant difference observed between the OKCs and dentigerous cysts (P=0.083). Conclusion: Patient age and lesion size differed significantly among lesion types associated with IMTs, with younger age and larger lesions for OKCs and odontogenic tumors. OKCs are likely to have a larger mesiodistal width than dentigerous cysts. The buccolingual width of ameloblastomas was larger than those of dentigerous cysts and OKCs.

Synthesis, Antiproliferative Activity and Molecular Docking Analysis of Both Enantiomerically Pure Decursin Derivatives as Anticancer Agents.

Using (S)-decursinol isolated from root of Angelica gigas Nakai (AGN), we semi-synthesized and evaluated a series of both enantiomerically pure decursin derivatives for their antiproliferative activities against A549 human lung cancer cells. All synthesized compounds showed a broad spectrum of inhibitory activities against the growth of A549 cells. Especially, compound (S)-2d with (E)-(furan-3-yl)acryloyl group showed the most potent activity (IC50: 14.03 µM) against A549 cancer cells as compared with the reference compound, decursin (IC50: 43.55 µM) and its enantiomer, (R)-2d (IC50: 151.59 µM). Western blotting assays indicated that (S)-2d more strongly inhibited Janus kinase 1 (JAK1) and signal transducer and activator of transcription activation 3 (STAT3) phosphorylation than decursin in a dose-dependent manner, while having no effect on CXCR7 overexpression and total STAT3 level. In addition, (S)-2d induced cell cycle arrest at G1 phase and subsequent apoptotic cell death in A549 cancer cells. Our combined analysis of molecular docking studies and biological data suggests that the inhibition of JAK1 with (S)-2d resulted in loss of STAT3 phosphorylation and inhibition of cell growth in A549 cancer cells. These overall results strongly suggest that (S)-2d (MRC-D-004) as a novel JAK1 inhibitor may have therapeutic potential in the treatment of A549 human lung cancers by targeting the JAK1/STAT3 signaling pathway.

Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach.

BACKGROUND: For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The "swing approach" that involves lip splitting of the mandible and temporary mandibular osteotomy and the "visor approach" that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients. MATERIALS AND METHODS: From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients' sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher's exact t-test. RESULT: There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group. CONCLUSION: There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.

Fibular free flap with proximal perforator skin paddle due to aberrant anatomy - a case report.

BACKGROUND: The fibular free flap is considered one of the most valuable options for mandible reconstruction. A perforator flap has gained widespread acceptance in oral and maxillofacial reconstruction. Typically, the fibula flap is obtained primarily with the distal perforator due to its reliable blood supply, with less attention given to the proximal perforators during the harvesting process. Normally, the distal perforator of the fibula exhibits stability and shows limited anatomical variations. However, there have been reported cases in which the distal perforator is absent. At times, these vascular abnormalities remain undetectable through Doppler examination or preoperative angiography evaluation. Therefore, this case details the experience of encountering the rare event of vascular abnormality in oral cancer surgery. CASE PRESENTATION: This article reports the case of a patient who presented with a congenital absence of the distal perforator in the peroneal artery, attributed to a vascular abnormality. Additionally, we provide a review of the concept of utilizing the proximal perforator as an alternative approach in the flap harvesting process. CONCLUSIONS: While the distal perforator of the peroneal artery is typically utilized for fibula free flap procedures, surgeons must remain cognizant of the potential for its absence due to aberrant anatomy. Recognizing an alternative approach in such cases can be pivotal for precise surgical planning and favorable outcomes in oral and maxillofacial reconstruction.

Antioxidant and Inhibitory Activities of Filipendula glaberrima Leaf Constituents against HMG-CoA Reductase and Macrophage Foam Cell Formation.

In our search for bioactive components, various chromatographic separations of the organic fractions from Filipendula glaberrima leaves led to the isolation of a new ellagitannin and a triterpenoid, along with 26 known compounds. The structures of the isolates were determined based on their spectroscopic properties and chemical evidence, which were then evaluated for their antioxidant activities, inhibitory activities on 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and foam cell formation in THP-1 cells to prevent atherosclerosis. Rugosin B methyl ester (1) showed the best HMG-CoA reductase inhibition and significantly reduced ox-low-density lipoprotein-induced THP-1 macrophage-derived foam cell formation at 25 µM. In addition, no cytotoxicity was observed in THP-1 cells at 50 µg/mL of all extracts in the macrophage foam cell formation assay. Therefore, F. glaberrima extract containing 1 is promising in the development of dietary supplements due to its potential behavior as a novel source of nutrients for preventing and treating atherosclerosis.

Therapeutic role of 2-stearoxyphenethyl phosphocholine targeting microtubule dynamics and Wnt/ß-catenin/EMT signaling in human colorectal cancer cells.

The inhibition of cell death, perturbation of microtubule dynamics, and acceleration of Wnt/ß-catenin/epithelial-mesenchymal transition (EMT) signaling are fundamental processes in the progression and metastasis of colorectal cancer (CRC). To explore the role of 2-stearoxyphenethyl phosphocholine (stPEPC), an alkylphospholipid-based compound, in CRC, we conducted an MTT assay, cell cycle analysis, western blot analysis, immunoprecipitation, immunofluorescence staining, Annexin V/propidium iodide double staining, small interfering RNA gene silencing, a wound-healing assay, an invasion assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the human CRC cell lines HT29 and HCT116. stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20). These results suggest that activation of the mitotic checkpoint complex and tubulin polymerization occurred, resulting in mitotic catastrophe in HT29 and HCT116 cells. In addition, stPEPC attenuated cell migration and invasion by regulating proteins mediated by EMT, such as E-cadherin and occludin. stPEPC altered the protein expression of Wnt3a and phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase 3ß (GSK3ß), and ß-catenin as well as their target genes, including cMyc and cyclin D1, in CRC cells. Thus, stPEPC may be useful for developing new drugs to treat human CRC.

Oleanolic acid alleviates the extrapyramidal symptoms and cognitive impairment induced by haloperidol through the striatal PKA signaling pathway in mice.

Haloperidol, one of the representative typical antipsychotics, is on the market for schizophrenia but shows severe adverse effects such as extrapyramidal symptoms (EPS) or cognitive impairments. Oleanolic acid (OA) is known to be effective for tardive dyskinesia which is induced by long-term treatment with L-DOPA. This study aimed to investigate whether OA could ameliorate EPS or cognitive impairment induced by haloperidol. The balance beam, catalepsy response, rotarod and vacuous chewing movement (VCM) tests were performed to measure EPS and the novel object recognition test was used to estimate haloperidol-induced cognitive impairment. Levels of dopamine and acetylcholine, the phosphorylation levels of c-AMP-dependent protein kinase A (PKA) and its downstream signaling molecules were measured in the striatum. OA significantly attenuated EPS and cognitive impairment induced by haloperidol without affecting its antipsychotic properties. Valbenazine only ameliorated VCM. Also, OA normalised the levels of dopamine and acetylcholine in the striatum which were increased by haloperidol. Furthermore, the increased phosphorylated PKA, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) levels and c-FOS expression level induced by haloperidol were significantly decreased by OA in the striatum. In addition, cataleptic behaviour of haloperidol was reversed by sub-effective dose of H-89 with OA. These results suggest that OA can alleviate EPS and cognitive impairment induced by antipsychotics without interfering with antipsychotic properties via regulating neurotransmitter levels and the PKA signaling pathway in the striatum. Therefore, OA is a potential candidate for treating EPS and cognitive impairment induced by antipsychotics.

Stereoselective synthesis of 1,6-diazecanes by a tandem aza-Prins type dimerization and cyclization process.

We report the stereocontrolled synthesis of 1,6-diazecanes via a tandem aza-Prins type reaction of N-acyliminium ions with allylsilanes. It involves an aza-Prins type dimerization and cyclization in a single-step operation. This reaction represents the first example of 10-membered N-heterocycle synthesis using an aza-Prins reaction. Also, the interesting formation of an unusual tetracyclic compound through further cyclization of 1,6-diazecane and bicyclic compounds by the intramolecular cyclization of linear allylsilane are described. This tandem aza-Prins protocol provides a new synthetic strategy for the direct synthesis of medium-sized nitrogen heterocycles.

Cystic lesion between a deciduous tooth and the succeeding permanent tooth: a retrospective analysis of 87 cases.

Objectives: The purpose of this study is to investigate the characteristics of dentigerous and radicular cysts that occur between deciduous and succeeding permanent teeth and to propose considerations for differential diagnosis of cysts at the treatment planning stage in the outpatient clinic. Materials and Methods: A total of 87 patients with a cystic lesion located between a deciduous tooth and the succeeding permanent tooth participated in the study. Twelve variables were analyzed to diagnose such a cyst. For data analysis, Fisher's exact test was used to determine the statistical significance of the variables. Results: Of the total 87 patients who participated in this study, 69 were diagnosed with dentigerous cysts and 18 were diagnosed with radicular cysts. Seven of the 12 differential factors analyzed in this study were statistically significant: age, location, symptoms, dental caries, endodontic treatment, delayed eruption, and size. Conclusion: Several criteria can be considered for diagnosis of dentigerous cysts or radicular cysts. Age, location, presence of symptoms and dental caries, previous endodontic treatment, cystic size, and delayed eruption of impacted permanent teeth are reliable factors that should be considered when diagnosing dentigerous and radicular cysts.

In vitro and in vivo neuroprotective effect of novel mPGES-1 inhibitor in animal model of Parkinson's disease.

mPGES-1 is found to be up-regulated in the dopaminergic neurons of the substantia nigra pars compacta (SNpc) of postmortem brain tissue from Parkinson's disease (PD) patients and neurotoxin 6-hydroxydopamine (6-OHDA)-induced PD mice. Since the genetic deletion of mPGES-1 abolished 6-OHDA-induced PGE2 production and 6-OHDA-induced dopaminergic neurodegeneration in vitro and in vivo models, mPGES-1 enzyme has the potential to be an important target for PD therapy. In the present work, we investigated whether a small organic molecule as mPGES-1 inhibitor could exhibit the neuroprotective effects against 6-OHDA-induced neurotoxicity in in vitro and in vivo models. For this research goal, a new series of arylsulfonyl hydrazide derivatives was prepared and investigated whether these compounds may protect neurons against 6-OHDA-induced neurotoxicity in both in vitro and in vivo studies. Among them, compound 7s (MPO-0144) as a mPGES-1 inhibitor (PGE2 IC50 = 41.77 nM; mPGES-1 IC50 = 1.16 nM) exhibited a potent neuroprotection (ED50 = 3.0 nM) against 6-OHDA-induced in PC12 cells without its own neurotoxicity (IC50 = >10 µM). In a 6-OHDA-induced mouse model of PD, administration of compound 7s (1 mg/kg/day, for 7 days, i.p.) ameliorated motor impairments and dopaminergic neuronal damage. These significant biological effects of compound 7s provided the first pharmacological evidence that mPGES-1 inhibitor could be a promising therapeutic agent for PD patients.

Pim-2 regulates bone resorptive activity of osteoclasts via V-ATPase a3 isoform expression in periodontal disease.

Cytoplasmic serine/threonine Pim kinases have emerged as important modulators of immune regulation and oncology. However, their regulatory roles in bone remodeling remain obscure. Here, we aimed to determine the roles of Pim kinases in periodontal disease (PD), focusing on the regulation of osteoclastogenesis and bone resorptive activity. We investigated Pim kinases expression in PD by analyzing data from the online Gene Expression Omnibus database and using ligature-induced periodontitis mouse model. The expression of Pim kinases during receptor activator of nuclear factor kB ligand (RANKL)-induced osteoclastogenesis was assessed in mouse bone marrow-derived macrophages (BMMs) using reverse transcription polymerase chain reaction. Osteoclast differentiation and bone resorption activity were respectively verified by tartrate-resistant acid phosphatase staining and dentin disc-based bone resorption assays. We silenced and overexpressed Pim-2 using small interfering RNA (siRNA) and retroviral vector, respectively, to investigate the molecular mechanisms underlying Pim-2 regulation in RANKL-induced osteoclastogenesis and bone resorption activity. Upregulated expression of Pim-2 was observed in both patients with PD and periodontitis-affected mouse gingival tissues. siRNA-mediated silencing of Pim-2 in BMMs diminished RANKL-induced resorptive activity without affecting osteoclastogenesis. Moreover, RANKL-triggered stimulation of a3 isoform, which is a subunit of vacuolar-type ATPase, was selectively attenuated in BMMs on silencing Pim-2. The overexpression of Pim-2 with a retroviral vector stimulated the a3 subunit, thus inducing bone resorption activity. Taken together, these results suggest that Pim-2 acts as a major modulator of osteoclastic activity by regulating a3 isoform expression in PD.

Cemento-osseous dysplasia: clinical presentation and symptoms.

Objectives: The purpose of this study was to evaluate risk factors and symptoms in cemento-osseous dysplasia (COD) patients. Materials and Methods: In this study, 62 patients who were diagnosed histologically with COD were investigated from 2010 to 2020 at the author's institution. We compared clinical and radiological characteristics of symptomatic and asymptomatic patients. The factors were sex, age, lesion size, site, radiologic stage of lesion, apical involvement, sign of infection, and history of tooth extraction. Statistical analysis was performed using Fisher's exact test and the chi-square test. Results: COD was more prevalent in female patients. With the exception of three cases, all were focal COD. The majority of patients presented with symptoms when the lesion was smaller than 1.5 cm in size. Symptoms were observed when the apex of the tooth was included in the lesion or there was a local infection around the lesion. The history of tooth extraction and previous endodontic treatment were evaluated, and history was not a significant predictor for the onset of symptoms. Conclusion: In this study, risk factors associated with symptomatic patients were size of lesion, apical involvement, and local infection.

Inducible Prostaglandin E Synthase as a Pharmacological Target for Ischemic Stroke.

As the inducible terminal enzyme for prostaglandin E2 (PGE2) synthesis, microsomal PGE synthase-1 (mPGES-1) contributes to neuroinflammation and secondary brain injury after cerebral ischemia via producing excessive PGE2. However, a proof of concept that mPGES-1 is a therapeutic target for ischemic stroke has not been established by a pharmacological strategy mainly due to the lack of drug-like mPGES-1 inhibitors that can be used in relevant rodent models. To this end, we recently developed a series of novel small-molecule compounds that can inhibit both human and rodent mPGES-1. In this study, blockade of mPGES-1 by our several novel compounds abolished the lipopolysaccharide (LPS)-induced PGE2 and pro-inflammatory cytokines interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α) in mouse primary brain microglia. Inhibition of mPGES-1 also decreased PGE2 produced by neuronal cells under oxygen-glucose deprivation (OGD) stress. Among the five enzymes for PGE2 biosynthesis, mPGES-1 was the most induced one in cerebral ischemic lesions. Systemic treatment with our lead compound MPO-0063 (5 or 10 mg/kg, i.p.) in mice after transient middle cerebral artery occlusion (MCAO) improved post-stroke well-being, decreased infarction and edema, suppressed induction of brain cytokines (IL-1ß, IL-6, and TNF-α), alleviated locomotor dysfunction and anxiety-like behavior, and reduced the long-term cognitive impairments. The therapeutic effects of MPO-0063 in this proof-of-concept study provide the first pharmacological evidence that mPGES-1 represents a feasible target for delayed, adjunct treatment - along with reperfusion therapies - for acute brain ischemia.

Effect of Observer's Sex and Chin Prominences on the Perception of the Lower Lip-Chin Prominence Angle.

ABSTRACT: This study aimed to identify the preferred range of lower lip-chin prominence angles in the Korean population and evaluate the effect of the individual lower lip-chin prominence angle on perceptions of esthetic chin profile.Chin prominence silhouettes were used to assess the lower lip-chin prominence preference. The observers randomly categorized each image as (1) normal, (2) slightly abnormal but not requiring surgical correction, and (3) abnormal and requiring surgery. Individual lower-chin prominence angles of all observers were analyzed using standardized clinical photographs.The normal range of lower lip-chin prominence angle is 0° to 25°; socially acceptable range is 0° to -10°, 25° to 40°; range needing surgery is -10° to -30° and 40° to 45°. Women are more tolerant to chin protrusion. A protrusive chin is more acceptable in observers with retrusive chin profile.Skeletal Class II profile is more acceptable than skeletal Class III in the Korean population. The individual lower-chin prominence angle could affect perception of desired surgery. These findings indicate that patient-specific treatment planning is important in achieving satisfaction in chin surgery.

Effects of photobiomodulation on bone remodeling in an osteoblast-osteoclast co-culture system.

The general bone anabolic effect of photobiomodulation (PBM) is largely accepted. As a result, PBM therapy is expected to be beneficial in the medical fields of dentistry and bone healing. However, most of the previous in vitro studies on PBM and bone metabolism were performed with single-cell cultures of osteoclast-lineage cells or osteoblast-lineage cells. In the present study, the bone-modulating effects of PBM were evaluated in an in vitro osteoblast/osteoclast co-culture system. Mouse bone marrow-derived macrophages (BMMs) and mouse calvarial pre-osteoblasts cells were purified and used as precursor cells for osteoclasts and osteoblasts, respectively. The PBM effects on single-cell culture of osteoclasts or osteoblasts as well as co-culture were examined by 1.2 J/cm2 low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; spot size, 1cm2; NDLux, Seoul, Korea) irradiation for 30 s at daily intervals throughout culture period. At the end of culture, the osteoclast differentiation and osteoblast differentiation were assessed by TRAP staining and ALP staining, respectively. The expressions of osteoclastogenic cytokines were evaluated by RT-PCR and Western blot analyses. Under the single-cell culture condition, PBM enhanced osteoblast differentiation but had minor effects on osteoclast differentiation. However, in the co-culture condition, its osteoblastogenic effect was maintained, and osteoclast differentiation was substantially reduced. Subsequent RT-PCR analyses and western blot results revealed marked reduction in receptor activator of NF-κB ligand (RANKL) expression and elevation in osteoprotegerin (OPG) expression by PBM in co-cultured cells. More importantly, these alterations in RANKL/OPG levels were not observed under the single-cell culture conditions. Our results highlight the different effects of PBM on bone cells based on culture conditions. Further, our findings suggest the indirect anti-osteoclastogenic effect of PBM, which is accompanied by a decrease in RANKL expression and an increase in OPG expression.

Idiopathic bone cavity: clinical and radiological features of 90 retrospective cases and surgical treatment.

OBJECTIVES: The purpose of this study was to evaluate the clinical and radiographic characteristics of idiopathic bone cavity (IBC) to determine the effect of surgical intervention on the process of healing. MATERIALS AND METHODS: All cases diagnosed with IBC during the period of 2011 to 2020 at our Department of Oral and Maxillofacial Surgery were searched. Ninety cases were retrieved. The features evaluated were sex, age, contour of the lesion, number of teeth involved, site, history of trauma, and postoperative healing pattern. The significance of differences was assessed by Mann-Whitney U test and chi-square test. RESULTS: The female:male ratio showed no predilection toward either sex (0.9:0.8). The mean age of the collected sample was 22.05±14.38 years, and the age ranged from 10 to 58 years. All cases presented in the mandible and showed well-circumscribed radiolucency. Margins were either scalloped or round in shape, and the size varied from one tooth to six teeth involvement. Seventy cases involved three or fewer roots. Three cases showed bilateral lesion. Four cases had a history of trauma at the area of the lesion. Fifty-one cases were followed for six months after surgery, and all showed increased bone density at the lesion. CONCLUSION: There is no definitive radiological or clinical feature of IBC. Considering the diversity of clinical and radiological features, such a diagnosis relies primarily on surgical findings of an empty bone cavity with no epithelial lining. Our data suggest that surgical intervention be the first choice of treatment as opposed to observation.

Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells.

We previously reported the anticancer activity of 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N'-methylpropylamino]-3,4-dihydroquinazoline (OZ-001), a T-type calcium channel (TTCC) blocker, against non-small cell lung cancer (NSCLC) in vitro and in vivo. Here, we evaluated the synergistic effect of OZ-001 and cisplatin on A549 human lung cancer cells and A549 xenograft mice. Our study demonstrated that treatment with OZ-001 and cisplatin sensitized A549 cells to cisplatin and significantly inhibited cell growth, increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and induced poly (ADP-ribose) polymerase (PARP) cleavage in A549 cells and an A549 xenograft tumor mouse model. Moreover, our findings showed that mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and signal transducer and activator of transcription (STAT3) inactivation was required for apoptosis induced by the combination of OZ-001 and cisplatin in in vitro and in vivo experiments. Our results suggest that combined treatment with OZ-001 and cisplatin could potentiate antiproliferative effects via suppression of the mTOR/p70S6K and STAT3 pathways and may be considered a potential therapeutic agent for NSCLC.

Discovery of N-amido-phenylsulfonamide derivatives as novel microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors.

Our previous research showed that N-carboxy-phenylsulfonyl hydrazide (scaffold A) could reduce LPS-stimulated PGE2 levels in RAW 264.7 macrophage cells by an inhibition of mPGES-1 enzyme. However, a number of scaffold A derivatives showed the drawbacks such as the formation of regioisomers and poor liver metabolic stability. In order to overcome these synthetic and metabolic problems, therefore, we decided to replace N-carboxy-phenylsulfonyl hydrazide (scaffold A) with N-carboxy-phenylsulfonamide (scaffold B) or N-amido-phenylsulfonamide frameworks (scaffold C) as a bioisosteric replacement. Among them, MPO-0186 (scaffold C) inhibited the production of PGE2 (IC50: 0.24 µM) in A549 cells via inhibition of mPGES-1 (IC50: 0.49 µM in a cell-free assay) and was found to be approximately 9- and 8-fold more potent than MK-886 as a reference inhibitor, respectively. A molecular docking study theoretically suggests that MPO-0186 could inhibit PGE2 production by blocking the PGH2 binding site of mPGES-1 enzyme. Furthermore, MPO-0186 demonstrated good liver metabolic stability and no significant inhibition observed in clinically relevant CYP isoforms except CYP2C19. This result provides a potential starting point for the development of selective and potent mPGES-1 inhibitor with a novel scaffold.

Primary repair of untreated cleft palate in an elderly patient: a case report.

Untreated adult or elderly cleft lip and palate patients are rarely seen, but studies on delayed primary palatal closure have been performed in the less developed Asian and African countries, where access to medical care is difficult. A 64-year-old woman visited our clinic with untreated cleft palate with a 40×20-mm-wide defect in the medial palate. Two-flap palatoplasty under general anesthesia was performed to close the cleft palate. After 1 month, the result was favorable without any complications including oronasal fistula. Cleft palate primary repair in an elderly patient is rare and has some surgical problems that are associated with a wide range of defects, but good results can be obtained if surgery is performed well with appropriate considerations.