In some fibroblasts, casein kinase 1α (CK1α) is localized to nuclear speckles, which are sub-nuclear compartments supplying splicing factors, whereas it is recruited on keratin filaments in ...colorectal cancer cells such as DLD1 cells. In order to obtain a deeper understanding of why CK1α is localized to these different subcellular sites, we herein elucidated the mechanisms underlying its localization to nuclear speckles. CK1α and FAM83H were localized to nuclear speckles in RKO and WiDr colorectal cancer cells, which do not express simple epithelial keratins, and in DLD1 cells transfected with siRNAs for type I keratins. The localization of FAM83H to nuclear speckles was also detected in colorectal cancer cells with a poorly organized keratin cytoskeleton in colorectal cancer tissues. Using an interactome analysis of FAM83H, we identified SON, a protein present in nuclear speckles, as a scaffold protein to which FAM83H recruits CK1α. This result was supported by the knockdown of FAM83H or SON delocalizing CK1α from nuclear speckles. We also found that CK1δ and ε are localized to nuclear speckles in a FAM83H-dependent manner. These results suggest that CK1 is recruited to nuclear speckles by FAM83H and SON in the absence of an intact keratin cytoskeleton.
Few reports exist on the changes associated with mandibular advancement surgery and on the effects of genioplasty. We investigated the combination of genioplasty and mandibular advancement surgery in ...surgical orthodontic therapy for maxillary protrusion with mandibular retrognathism. A total of 17 patients (2 men and 15 women) between 17 and 32 years of age at the first visit who were diagnosed with maxillary protrusion with mandibular retrognathism, and who underwent mandibular advancement surgery at the Okashita Orthodontic Office for 6 years from 2013 to 2018 were included in the study, eight women underwent only sagittal split ramus osteotomy (the SSRO group), while 2 men and 7 women underwent combined SSRO and genioplasty (the SSRO+GP group). Cephalograms from the first visit and those taken within 3 months following the operation were evaluated.Our study suggested that the anterior-posterior diameter of the pharyngeal airway increases when genioplasty is combined with mandibular advancement surgery in patients with maxillary protrusion. Patients with maxillary protrusion and mandible retrognathism tend to have narrow pharyngeal airways, and are reportedly more susceptible to sleep disorders with increasing age. Therefore, genioplasty should be considered not only for the improvement of the facial profile, but for functional reasons as well. (J Osaka Dent Univ 2022; 56: 167-173)
Background:Hyperuricemia induces endothelial dysfunction, oxidative stress and inflammation, increasing cardiovascular morbidities. It also raises the incidence of atrial fibrillation; however, ...underlying mechanisms are unknown.Methods and Results:The effects of urate on expression of Kv1.5 in cultured mouse atrial myocytes (HL-1 cells) using reverse transcriptase-PCR, immunoblots, flow cytometry and patch-clamp experiments were studied. Treatment with urate at 7 mg/dl for 24 h increased the Kv1.5 protein level, enhanced ultra-rapid delayed-rectifier K+channel currents and shortened action potential duration in HL-1 cells. HL-1 cells expressed the influx uric acid transporter (UAT), URATv1, and the efflux UATs, ABCG2 and MRP4. An inhibitor against URATv1, benzbromarone, abolished the urate effects, whereas an inhibitor against ABCG2, KO143, augmented them. Flow cytometry showed that urate induced an increase in reactive oxygen species, which was abolished by the antioxidant, N-acetylcysteine (NAC), and the NADPH-oxidase inhibitor, apocynin. Both NAC and apocynin abolished the enhancing effects of urate on Kv1.5 expression. A urate-induced increase in the Kv1.5 proteins was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK), and was abolished by an ERK inhibitor, PD98059. NAC abolished phosphorylation of ERK by urate.Conclusions:Intracellular urate taken up by UATs enhanced Kv1.5 protein expression and function in HL-1 atrial myocytes, which could be attributable to ERK phosphorylation and oxidative stress derived from nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase. (Circ J 2015; 79: 2659–2668)
Heat shock proteins (Hsps) are overexpressed in several tumors and contribute to cell proliferation, metastasis, and anticancer drug resistance. Therefore, Hsp inhibitors have enhanced cytotoxicity ...as chemotherapeutic agents and may be effective with a reduced dosage for tumor therapy to avoid side effects.
Four new azaphilones, maximazaphilones I-IV (1-4), and three known compounds (5-7) have been isolated from the airborne-derived fungus Penicillium maximae. Inhibitory effects of isolated compounds against induction of Hsp105 were evaluated by the luciferase assay system using Hsp105 promoter. In this assay, 2-4, 6, and 7 significantly inhibited hsp105 promoter activity without cytotoxicity. In addition, all isolated compounds except for 5 significantly induced the death of Adriamycin (ADR)-treated HeLa cells. Interestingly, 1-4, 6, and 7 didn't show anti-proliferative and cell death-inducing activity without ADR.
This study revealed the chemical structures of maximazaphilones I-IV (1-4) and the potency of azaphilones may be useful for cancer treatment and reducing the dose of anticancer agents. In addition, one of the mechanisms of cell death-inducing activity for 2-4, 6, and 7 was suggested to be inhibitory effects of Hsp105 expression.
Anaplastic lymphoma kinase (ALK) is a receptor-type tyrosine kinase that promotes cell growth upon stimulation with ligands such as midkine and pleiotrophin. Recently, a truncated isoform of ALK was ...identified in a variety of tumors. This isoform is expressed from a novel ALK transcript initiated from a de novo alternative transcription initiation (ATI) site in ALK intron 19 (referred to as ALKATI). ALKATI, which consists of only the intracellular kinase domain, localizes to the nucleus as well as the cytoplasm. However, its nuclear role is unknown. In this study, we determined that ALKATI promoted chromatin structural changes in the nucleus in a kinase activity-dependent manner. We found that expression of ALKATI increased the level of the heterochromatin marker Lys9 tri-methylated histone H3. In addition, we demonstrated that ALKATI phosphorylated the nuclear protein A-kinase anchoring protein 8 (AKAP8) and altered its subcellular localization from the insoluble fraction to the soluble fraction. These results suggest that ALKATI induces chromatin structural changes and heterochromatinization through phosphorylation of AKAP8 in the nucleus.
FAM83H is essential for the formation of dental enamel because a mutation in the FAM83H gene causes amelogenesis imperfecta (AI). We previously reported that the overexpression of FAM83H often occurs ...and disorganizes the keratin cytoskeleton in colorectal cancer cells. We herein show that FAM83H regulates the organization of the keratin cytoskeleton and maintains the formation of desmosomes in ameloblastoma cells. FAM83H is expressed and localized on keratin filaments in human ameloblastoma cell lines and in mouse ameloblasts and epidermal germinative cells in vivo. FAM83H shows preferential localization to keratin filaments around the nucleus that often extend to cell-cell junctions. Alterations in the function of FAM83H by its overexpression, knockdown, or an AI-causing truncated mutant prevent the proper organization of the keratin cytoskeleton in ameloblastoma cells. Furthermore, the AI-causing mutant prevents desmosomal proteins from being localized to cell-cell junctions. The effects of the AI-causing mutant depend on its binding to and possible inhibition of casein kinase I (CK-1). The suppression of CK-1 by its inhibitor, D4476, disorganizes the keratin cytoskeleton. Our results suggest that AI caused by the FAM83H mutation is mediated by the disorganization of the keratin cytoskeleton and subsequent disruption of desmosomes in ameloblasts.
We used cephalograms to investigate the Wits appraisal to analyze the skeletal Class I Japanese adults with individualized normal occlusion. The average Wits appraisal values in this study were -0.79 ...mm for males and -2.05 mm for females. In the group of males in whom Wits appraisal measurements were above the mean value, the mean and standard deviation values for maxillofacial morphology were as follows: ∠ANB, 2.95±0.52; ∠Occl to SN, 14.88±3.47; ∠GoGn to SN, 30.75±4.43; and FMA, 25.44±3.62. The corresponding values for the below‐average were as follows: ∠ANB, 2.52±0.74; ∠Occl to SN, 16.40±3.34; ∠GoGn to SN, 30.72±4.02; and FMA, 25.74±3.57. In the group of females in whom Wits appraisal measurements were above the mean value, the mean and standard deviation values for maxillofacial morphology were as follows: ∠ANB, 2.59±0.76; ∠Occl to SN, 16.77±3.89; ∠GoGn to SN, 33.74±5.36; and FMA was 28.52±3.56. The corresponding values for the below‐average were as follows: ∠ANB, 2.55±0.63; ∠Occl to SN, 19.00±4.25; ∠GoGn to SN, 34.91±4.28; and FMA, 29.12±3.26. When performing orthodontic treatment, Wits appraisal measurement is an effective method for evaluating the anteroposterior positional relationship of the maxillary and mandibular alveolar bases. However, Wits appraisal alone may lead to misidentification. This suggests that for accurate evaluation of maxillofacial morphology, it is necessary to use ∠ANB in conjunction with the recognition of the mutually compensatory relationship between teeth and maxillofacial components. (J Osaka Dent Univ 2024; 58: 333-338)
This study explores the relationship between mandibular symphysis morphology and orthodontic evaluations in individuals with skeletal Class II malocclusion. The mandibular symphysis, a significant ...aesthetic and functional component of the lower face, has implications for treatment decisions and tooth mobility. By analyzing lateral cephalograms, the research identifies key measurement points and angles to assess both craniofacial and symphysis characteristics. Notable gender differences are observed, impacting craniofacial and symphysis features, with correlations identified between craniofacial morphology, vertical position, inclination of the anterior teeth, and symphysis inclination. This study underscores the importance of understanding the intricate interplay between mandibular symphysis morphology and the treatment of orthodontic evaluations in skeletal Class II malocclusion cases. These insights can inform treatment planning, enhance orthodontic interventions, and contribute to improved outcomes. (J Osaka Dent Univ 2024; 58: 41-49)
We investigated the morphology of the sella turcica in Japanese adults with skeletal Class I craniofacial morphological. The sella turcica is an important reference point in orthodontic treatment ...planning and growth evaluation. The participants were 47 males and 43 females who were fifth-year students at Osaka Dental University with normal occlusion and craniofacial morphology. The sella turcica morphology and craniofacial morphology were studied using cephalometric radiographs. Results showed gender variations in the sella turcica size. The most prevalent morphology in both males and females was a nomal sella turcica. Correlations were found between the sella turcica size and certain craniofacial morphology measurements. Ethnic differences in the sella turcica size were observed, highlighting the importance of understanding normal sella turcica morphology when detecting abnormalities. This study provides valuable insights into the sella turcica's characteristics in Japanese adults with skeletal Class I craniofacial morphology, contributing to better treatment planning and understanding of craniofacial development. Further research during growth stages should shed light on its relation to the craniofacial morphology of the abnormalities. (J Osaka Dent Univ 2024; 58: 13-19)
Using Steiner analysis we examined the facial characteristics of 35 male and 35 female Chinese adults with maxillary protrusion selected from a clinic in New Taipei City. Angular and linear ...measurements were determined. In comparison with pre-existing measurement values for Chinese children, the SNA angle, SNB angle, SND angle, L1 to NB (angle), Interincisal angle, and SL values for our subjects were significantly greater while the U1 to NA (mm), U1 to NA (angle), and SE values were significantly smaller. Compared to measurement values for Japanese, the SNA angle, ANB angle, U1 to NA (mm), U1 to NA (angle), Pog to NB, and SE were larger, and the SNB angle, SND angle, Interincisal angle, Occl to SN, and SL were smaller. These results demonstrate that there was excessive growth in Chinese adults with maxillary protrusion. The mandibles showed retrusion, and the degree of clockwise rotation was found to be less than in Japanese. In addition, with respect to the occlusal plane, the inclination in Chinese was less than in Japanese. Based on the above findings, it was suggested that maxillary protrusion in Chinese adults is easier to treat than in Japanese. (J Osaka Dent Univ 2022; 56: 1-6)
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