Anti-inflammatory potential of remimazolam: A laboratory and clinical investigation.

BACKGROUND: Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti-inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti-inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti-inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches. METHODS: The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR. RESULTS: Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C-reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p = .014). CONCLUSIONS: Remimazolam exerted stronger anti-inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production.

Interaction effect between low birthweight and resistin gene rs1862513 variant on insulin resistance and type 2 diabetes mellitus in adulthood: Toon Genome Study.

AIMS/INTRODUCTION: Gene-environment interactions are considered to critically influence type 2 diabetes mellitus development; however, the underlying mechanisms and specific interactions remain unclear. Given the increasing prevalence of low birthweight (LBW) influenced by the intrauterine environment, we sought to investigate genetic factors related to type 2 diabetes development in individuals with LBW. MATERIALS AND METHODS: The interaction between 20 reported type 2 diabetes susceptibility genes and the development of type 2 diabetes in LBW (<2,500 g) individuals in a population-based Japanese cohort (n = 1,021) was examined by logistic regression and stratified analyses. RESULTS: Logistic regression analyses showed that only the G/G genotype at the rs1862513 locus of the resistin gene (RETN), an established initiator of insulin resistance, was closely related to the prevalence of type 2 diabetes in individuals with LBW. Age, sex and current body mass index-adjusted stratified analyses showed a significant interaction effect of LBW and the RETN G/G genotype on fasting insulin, homeostatic model assessment 2-insulin resistance, Matsuda index and the prevalence of type 2 diabetes (all P-values for interaction <0.05). The adjusted odds ratio for type 2 diabetes in the LBW + G/G genotype group was 7.33 (95% confidence interval 2.43-22.11; P = 0.002) compared with the non-LBW + non-G/G genotype group. Similar results were obtained after excluding the influence of malnutrition due to World War II. CONCLUSIONS: Simultaneous assessment of LBW and the RETN G/G genotype can more accurately predict the risk of future type 2 diabetes than assessing each of these factors alone, and provide management strategies, including early lifestyle intervention in LBW population.

Effectiveness of curcumin-based antimicrobial photodynamic therapy against Staphylococcus aureus.

PURPOSE: This study investigated the effectiveness of curcumin-based antimicrobial photodynamic therapy (aPDT) against Staphylococcus aureus (S. aureus), the causative agent of ventilator-associated pneumonia. METHODS: Curcumin was added to S. aureus culture medium at concentrations of 25, 2.5, and 0.25 µM. After 60 min (20-25°C), each culture was irradiated for 1 and 3 min, and viable bacteria were counted. Curcumin (25 µM) was also added to a bacterial suspension with D-mannitol and sodium azide; microbial counts were determined after irradiation for 3 min. RESULTS: S. aureus was significantly reduced in the 1-min (P = 0.043) and 3-min (P = 0.011) irradiation groups in comparison to the 0-min irradiation group with 25 µM curcumin. No significant differences were observed between the curcumin alone group and the curcumin plus D-mannitol or sodium azide group. CONCLUSION: The findings of this study indicate that prolonged exposure (≥1 min) of S. aureus to LED in 25 µM curcumin solution induces cell wall injury. Curcumin-based aPDT as an adjunct to conventional oral care, employing existing dentistry equipment, offers a promising approach that does not rely on antimicrobial drugs or allows the emergence of resistant bacterial strains. This suggests its potential role in future strategies aimed at preventing ventilator-associated pneumonia.

Testicular teratomagenesis from primordial germ cells with overexpression of germinal center-associated nuclear protein.

Testicular teratomas are the major histologic type of testicular germ cell tumors and their incidence continues to grow. Moreover, teratomas can develop from undifferentiated cells in induced pluripotent stem (iPS) cell transplantation therapy, seriously hampering the progress of regenerative medicine. Germinal center-associated nuclear protein (GANP) is thought to be important to the biogenetic control of primordial germ cells and is among the genes susceptible to testicular germ cell tumors. Thus, we analyzed the expression of GANP in human testicular postpubertal-type teratomas and established a novel mouse model to reveal the association between GANP and teratomagenesis. We analyzed 31 cases of human testicular postpubertal-type teratomas and, in all cases, GANP was overexpressed. The aberrant expression was also detected in germ cell neoplasia in situ accompanied by the teratoma. GANP expression was particularly high in the epithelia of the epidermis, cutaneous appendages, and trachea-like ciliated epithelium. To further clarify the association between GANP and teratomagenesis, we established a novel teratomagenesis mouse model (CAG-ganpTg mice). In the GANP-teratoma mice, GANP-overexpressing teratomas were more frequent at the testes and the middle portion of the uterus than has been seen in the previously established mouse models. In conclusion, GANP is overexpressed in testicular postpubertal-type teratomas and is an essential teratomagenic factor. We also found that CAG-ganpTg mice are useful mouse models of teratomagenesis that mimics human midline teratomas and that teratomas may originate from the overexpression of GANP in primordial germ cells.

Investigation of bactericidal effect of a mid-infrared free electron laser on Escherichia coli.

The rapid increase in the number of bacteria that are resistant to many commonly used antimicrobial agents and their global spread have become a major problem worldwide. In particular, for periodontal disease, which is a localized infection, there is a growing need for treatment methods that do not primarily involve antimicrobial agents, and antimicrobial photodynamic therapy (aPDT) is attracting attention. In this study, the bactericidal effects of a mid-infrared free electron laser (MIR-FEL) on E. coli were investigated as a basic study to examine the applicability of MIR-FELs, which can selectively excite molecular vibrations due to their wavelength tunability, to aPDT. The optimal irradiation wavelengths to be examined in this study were determined from the infrared spectrum of the bacteria, which was obtained using Fourier transform infrared spectroscopy. Five irradiation wavelengths (6.62, 6.88, 7.14, 8.09 and 9.26 µm) were selected from the FT-IR spectrum, and we found that the bactericidal effects at a wavelength of 6.62 µm were markedly stronger than those observed at the other wavelengths. At this wavelength corresponding to the Amide II band, the bacterial survival rate decreased significantly as the irradiation time increased. On the contrary, irradiation of a neodymium-doped yttrium aluminum garnet (Nd: YAG) laser at 1.06 µm exhibited no distinct bactericidal effect. No morphological changes were observed after MIR-FEL irradiation, suggesting that a bacterial organelle molecule may be the target of MIR-FEL irradiation, but the exact target was not identified. Furthermore, the temperature change induced in the culture medium by the laser irradiation was ± 1.5 °C at room temperature. These results suggest that the bactericidal effects of MIR-FEL are derived from photochemical reactions involving infrared photons, since E. coli is usually killed by heating it to 75 °C for 1 min or longer.

STAT3 Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung Disease in Patients With Renal Cell Carcinoma.

We evaluated the association of signal transducer and activator of transcription 3 (STAT3) polymorphisms with the incidence of mammalian target of rapamycin (mTOR) inhibitor-induced interstitial lung disease (ILD) in patients with renal cell carcinoma (RCC). We also used lung-derived cell lines to investigate the mechanisms of this association. Japanese patients with metastatic RCC who were treated with mTOR inhibitors were genotyped for the STAT3 polymorphism, rs4796793 (1697C/G). We evaluated the association of the STAT3 genotype with the incidence of ILD and therapeutic outcome. In the 57 patients included in the primary analysis, the ILD rate within 140 days was significantly higher in patients with the GG genotype compared with those with other genotypes (77.8% vs. 23.1%, odds ratio=11.67, 95% confidential interval=3.0644.46). There were no significant differences in progression-free survival or time-to-treatment failure between the patients with the GG genotype and those with other genotypes. An in vitro study demonstrated that some lung-derived cell lines carrying the GG genotype exhibited an increase in the expression of mesenchymal markers, such as fibronectin, N-cadherin, and vimentin, and decreases in E-cadherin, which is an epithelial marker associated with exposure to everolimus, although STAT3 expression and activity were not related to the genotype. In conclusion, the GG genotype of the STAT3 rs4796793 polymorphism increases the risk of mTOR inhibitor-induced ILD, supporting its use as a predictive marker for RCC.

Impact on Porphyromonas gingivalis of antimicrobial photodynamic therapy with blue light and Rose Bengal in plaque-disclosing solution.

OBJECTIVES: Antimicrobial photodynamic therapy (aPDT) in periodontal pockets using lasers is difficult to perform in some cases because of the high cost of irradiation equipment and the narrow irradiation field. The purpose of the present study was to examine the effects of aPDT in combination with a plaque-disclosing solution and blue light-emitting diode (LED), which are used for composite resin polymerization. METHODS: The reactive oxygen species generated by irradiating 0.001% RB or MB with blue light were analyzed using electron spin resonance spectroscopy. Blue-light exposure was performed at 6.92, 20.76 and 124.6 J. The microorganism to be sterilized was Porphyromonas gingivalis. After aPDT, colony-forming units (CFUs) were measured to estimate cell survival. Carbonylated protein (PC) levels were used to evaluate oxidative stress. All statistical analyses were performed with Tukey's multiple comparisons test or the unpaired t-test. RESULTS: Singlet oxygen (1O2) generation was confirmed by RB+blue LED. 1O2 production was significantly greater with the blue LED irradiation of RB than that of MB (p < 0.0001). CFUs were significantly lower in the blue LED-irradiated group than in the non-LED-irradiated group (p < 0.01). The bactericidal effect increased in a time-dependent manner. aPDT increased PC levels. No morphological changes were observed in P. gingivalis. CONCLUSIONS: The present results suggest that aPDT exerts bactericidal effects against P. gingivalis by increasing oxidative stress through the generation of 1O2 in cells. Periodontal disease may be treated by aPDT using the equipment available in dental offices.

Identification and Synthesis of DDI-6, a Quinolinol Analog Capable of Activating Both Caenorhabditis elegans and Mouse Spermatozoa.

Sperm activation is an essential process by which the male gametes become capable of fertilization. Because the process in Caenorhabditis elegans is readily reproducible in vitro, this organism serves as an excellent model to investigate it. C. elegans sperm activation in vivo occurs during spermiogenesis. Membranous organelles (MOs) contained within spermatids fuse with the plasma membrane, resulting in extracellular release of their contents and relocation of some proteins indispensable for fertilization from the MO membrane onto the sperm surface. Intriguingly, these cytological alternations are exhibited similarly in mouse spermatozoa during the acrosome reaction, which also represents a form of sperm activation, prompting us to hypothesize that C. elegans and mice share a common mechanism for sperm activation. To explore this, we first screened a chemical library to identify compounds that activate C. elegans spermatozoa. Because a quinolinol analog named DDI-6 seemed to be a candidate sperm activator, we synthesized it to use for further analyses. This involved direct dechlorination and hydrogenolysis of commercially available 5-chloro-8-quinolinol, both of which are key steps to yield 1,2,3,4-tetrahydro-8-quinolinol, and we subsequently introduced the sulfonamide group to the compound. When C. elegans spermatids were stimulated with solvent alone or the newly synthesized DDI-6, approx. 3% and approx. 28% of spermatids became MO-fused spermatozoa, respectively. Moreover, DDI-6 triggered the acrosome reaction in approx. 20% of mouse spermatozoa, while approx. 12% became acrosome-reacted after mock stimulation. Thus, DDI-6 serves as a moderately effective activator for both C. elegans and mouse spermatozoa.

Involvement of Nestin in the Progression of Canine Mammary Carcinoma.

Nestin, a class VI intermediate filament protein, is known to be expressed in various types of human neoplasms, including breast cancer, and is associated with their progression. However, its expression and role in canine mammary tumors remain unknown. We analyzed nestin expression in canine mammary tumors using in situ hybridization and immunohistochemistry. We also investigated its role in a canine mammary carcinoma cell line using RNA interference. Nestin expression was not observed in luminal epithelial cells of any of the 62 cases of benign mammary lesions examined, although myoepithelial cells showed its expression in most cases. In 16/50 (32%) primary mammary carcinomas and 6/15 (40%) metastases of mammary carcinomas, cytoplasmic nestin expression was detected in luminal epithelial cells. In luminal cells of primary mammary carcinomas, its expression was positively related to several pathological parameters that indicate high-grade malignancy, including histological grading (P < .01), vascular/lymphatic invasion (P < .01), Ki-67 index (P < .01), and metastasis (P < .05). Immunohistochemistry revealed that nestin expression was related to vimentin expression in mammary carcinomas (P < .01). This relationship was confirmed using reverse transcription-quantitative polymerase chain reaction using 9 cell lines derived from canine mammary carcinoma (P < .01). Finally, nestin knockdown in canine mammary carcinoma cells using small interfering RNA inhibited cell proliferation and migration based on WST-8, Boyden chamber, and cell-tracking assays. These findings suggest that nestin may at least partially mediate these behaviors of canine mammary carcinoma cells.

Sunitinib decreases the expression of KRT6A and SERPINB1 in 3D human epidermal models.

Hand-foot skin reaction (HFSR) is a common side effect caused by several tyrosine kinase inhibitors, including sunitinib. However, the nature of the cornifying factors related to the molecular biological mechanisms underlying HFSR remains poorly understood. We used human keratinocyte models to investigate the key cornifying factors for dermatological and biological abnormalities induced by sunitinib. On the basis of the results of microarray analysis using the three-dimensional (3D) human epidermal model, keratin (KRT)6A, serine protease inhibitor (SERPIN)B1, KRT5, and SERPIN Kazal-type 6 were selected as candidate genes related to HFSR. Sunitinib treatment significantly decreased the expression of SERPINB1 and KRT6A in the immunohistochemical staining of the 3D epidermal model. In PSVK1 cells, but not in normal human epidermal keratinocyte cells, both of which are human normal keratinocyte cell lines, sunitinib decreased the expression of KRT6A with a concomitant decrease in levels of phosphorylated extracellular signal-regulated kinases (ERK)1/2 and phosphorylated p38 mitogen-activated protein kinase (MAPK). Inhibitors of the ERK and p38 MAPK signal pathways also significantly decreased KRT6A expression. Sunitinib-induced decrease in KRT6A expression was suppressed by the inhibition of glycogen synthase kinase-3ß by enhancing ERK1/2 and p38 MAPK phosphorylation. Thus, sunitinib reduces the expression of KRT6A and SERPINB1 by inhibiting the ERK1/2 and p38 MAPK signalling pathways in the skin model. These changes in expression contribute to the pathology of HFSR.

Synthesis of peptide conjugates with vitamins for induction of antigen-specific immunotolerance.

In this report, we designed conjugates of an antigen peptide with the immunosuppressive vitamins all-trans retinoic acid (ATRA) and vitamin D3 for efficient induction of antigen-specific immunotolerance. We established a synthetic scheme for the preparation of the peptide-vitamin conjugates, which the chemically unstable vitamins tolerated. Among the obtained conjugates, the ATRA conjugate successfully suppressed inflammatory effects in macrophages and dendritic cells and induced antigen presentation in dendritic cells. This synthetic method of conjugate is conceivably applicable to other antigen peptides for induction of antigen-specific immunotolerance.

Biochemical Characterization of a Lipolytic Enzyme From Aspergillus oryzae That Hydrolyzes Triacylglycerol and Sterol Esters.

A novel lipolytic enzyme-encoding gene, lipO745, from Aspergillus oryzae RIB40 was cloned and expressed in Pichia pastoris. Purified recombinant LipO745 (rLipO745) had a molecular mass of approximately 60 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. rLipO745 exhibited maximum activity at 40 °C and pH 7.0 and was stable at temperatures ≤ 40 °C. The substrate specificity of purified rLipO745 was analyzed using α-naphthyl esters as artificial substrates and various triacylglycerol and sterol esters as natural substrates. From among a panel of α-naphthyl esters (C2-C16), α-naphthyl butyrate (C4), with an activity of 269 ± 3.3 units/mg protein, was the optimal substrate for hydrolysis by the purified recombinant protein. The Km and kcat values of rLiO745 for the C4 substrate were 0.073 ± 0.0012 mM and 608 ± 108 s-1, respectively. The purified recombinant enzyme had considerable hydrolytic activity toward tributyrin, tripalmitin, and triolein, indicating lipase activity, and toward cholesteryl acetate, butyrate, palmitate, and oleate, indicating sterol esterase activity. Transesterification activities between tributyrin and cholesterol or between tributyrin and campesterol were also determined.

Effect of physical stimulation (gingival massage) on age-related changes in gingival microcirculation.

The decline in circulatory function with aging may be alleviated by a combination of gingival massage (physical stimulation) and mechanical cleaning. Several studies have reported the systemic effect of physical stimulation on various parts of the body, including its therapeutic effect on pain in the neck and shoulders that becomes evident with age, and improvement in blood circulation. In contrast, few studies have reported on the changes in gingival microcirculation induced by gingival massage, while no previous study has evaluated the effect of gingival microcirculation on age-related changes in the hemodynamics of the oral cavity. This study aimed to investigate how gingival massage affects age-related changes in gingival microcirculation. Male Wistar rats (7-week, 6-month and 1-year old) were prepared for a gingival massage group and a control group. Mechanical stimulation was applied on the maxillary molar gingiva for 5 seconds twice a week for 4 weeks. Subsequently, gingival reactive hyperemia was measured using a laser Doppler flowmeter. In addition, morphological analyses were also performed by hematoxylin and eosin and Indian ink staining and a vascular resin cast model. Base Flow, maximum response (Peak), and time required for the maximum response to halve (T1/2) were reduced in 1-year-old rats compared with the other age groups. In the mechanical stimulated group, T1/2 was increased in 7-week, 6-month, and 1-year-old rats, and total blood flow (Mass) was increased in 6-month and 1-year-old rats. In addition, clear blood vessel networks and loop-like revascularization were only observed in the mechanical stimulated group. Changes in age-related decline in gingival microcirculatory function and vascular construction were reported in this study, and the results suggested that gingival massage activates both the functional and morphological aspects of gingival microcirculation and may be effective for maintaining oral health.

Low birthweight is associated with type 2 diabetes mellitus in Japanese adults: The Toon Health Study.

AIMS/INTRODUCTION: Low birthweight is reportedly associated with type 2 diabetes mellitus; however, this association has not been confirmed in the Japanese population, and whether high birthweight is associated with type 2 diabetes mellitus is controversial. We aimed to investigate the association between birthweight and type 2 diabetes mellitus among a general Japanese population. MATERIALS AND METHODS: Overall 1,135 middle- to old-aged Japanese men and women were enrolled in the Toon Health Study. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes mellitus, and a questionnaire survey about birthweight was administered. The association between birthweight and the prevalence of type 2 diabetes mellitus in later life of the participants was examined using multivariable logistic regression analysis. Stratified analysis by current body mass index was also carried out. RESULTS: The mean age was 56.5 ± 12.2 years. Type 2 diabetes mellitus was observed in 9.3% of the participants in this study. Compared with the reference group (2,500-3,999 g), the adjusted odds ratio of the low-birthweight group (<2,500 g) for type 2 diabetes mellitus was 2.46 (95% confidence interval 1.48-4.10). The association between the high-birthweight group (≥4000 g) and type 2 diabetes mellitus was not significant after including family history of diabetes in the multivariable model. The odds ratio of the low-birthweight group for type 2 diabetes mellitus was higher in the overweight/obese group than in the non-overweight group. CONCLUSIONS: Low birthweight was associated with an increased risk of type 2 diabetes mellitus in a Japanese population, especially in overweight/obese individuals.

[Historical changes in medical examinations for those engaged in specified work in Japan: Work covered and criteria].

OBJECTIVES: In Japan, so-called "medical examinations for those engaged in specified work" involve the same tests as those in general medical examinations, regardless of the type of work engaged in. The role of these medical examinations and "medical examinations with specified items for those engaged in harmful work operations" is also unclear. Therefore, questions have been raised about the appropriateness of the work covered by this medical examination. However, its legal system is complex and difficult to interpret. This study clarifies the changes in the type of work and their criteria covered by this medical examination. METHODS: We investigated laws and regulations, notifications, papers, and publications related to the history of medical examinations for those engaged in specified work. RESULTS: In 1947, Article 48 of the former ordinance on industrial safety and health stipulated that those engaged in work involving the handling of harmful substances that require special safety and health management shall undergo so-called "medical examinations for those engaged in specified work." Quantitative criteria for this work were indicated in a notification in 1948 in the form of tentative reference values, and they have not changed significantly since then. As a result, many of the standards used to determine who is subject to medical examinations for those engaged in specified work have exceeded allowable concentrations. CONCLUSION: The work covered by medical examinations for those engaged in specified work and its criteria have hardly been modified in approximately 70 years. In view of the changes in social environment and improvement in management methods for harmful work, it is necessary to rearrange the purposes and roles of the medical examinations with specified items for those engaged in harmful work operations and medical examinations for those engaged in specified work and to reconsider the method of the medical examinations for those engaged in specified work.

Singlet oxygen generated by a new nonthermal atmospheric pressure air plasma device exerts a bactericidal effect on oral pathogens.

Oral diseases generally have certain bacteria associated with them. Non-thermal atmospheric pressure plasma (NTAP), generated at atmospheric pressure and room temperature, incorporates several molecules, including reactive oxygen species, that can inactivate various bacteria including oral pathogens. For this reason, several NTAP devices have been developed to treat oral diseases. Use of noble gases can enhance the bactericidal efficacy of NTAP, but this requires additional gas supply equipment. Therefore, a new NTAP device that employs ambient air as the working gas was developed. The device generates non-thermal atmospheric pressure air plasma. Here, the singlet oxygen (1O2) levels generated, their bactericidal effects on oral pathogens (Streptococcus mutans, Porphyromonas gingivalis, and Enterococcus faecalis), and the bacterial oxidative stress they imposed were measured. 1O2 generation in phosphatebuffered saline was assessed qualitatively using electron spin resonance (ESR) spectroscopy, and bactericidal efficacy was evaluated by counting of colony-forming units/mL. Bacterial oxidative stress was determined by measurement of hydrogen peroxide (H2O2) and superoxide dismutase (SOD) activity. ESR indicated that the level of 1O2 increased significantly and time-dependently, and was inversely correlated with distance, but the bactericidal effects were correlated only with treatment time (not distance) as H2O2 increased and SOD levels decreased, suggesting that the new device has potential applicability for treatment of oral disease.

Antimicrobial photodynamic therapy using a plaque disclosing solution on Streptococcus mutans.

OBJECTIVES: Photodynamic therapy with a bactericidal action is called antimicrobial photodynamic therapy (aPDT),which is a method of staining an object with a photosensitizing dye and then sterilizing by irradiating the dye at it's excitation wavelength. In this study, we aimed to investigate a caries pathogenic bactericidal method in a site difficult to mechanically remove, by examining aPDT effect on Streptococcus mutans (S. mutans), which is a typical caries pathogenic bacteria by applying the plaque disclosing solution as photosensitizing dye. METHODS: The absorption wavelength spectrum of irradiating plaque staining agent phloxine B (PB) was analyzed using UV-vis. Reactive oxygen species (ROS) generated by photo excitation with blue LED irradiation was measured by electron spin resonance technique. S. mutans was cultured according to a conventional method and the effect of aPDT after PB staining was evaluated by a Colony Forming Unit (CFU). In addition, protein carbonyl (PC), an oxidative stress marker, was also measured by western blotting. RESULTS: Singlet oxygen was generated by PB with blue light. As a result of aPDT treatment on S. mutans under this condition, it was recognized that CFU was suppressed dependent on irradiation intensity of blue light. In addition, the expression of PC was enhanced by aPDT. CONCLUSIONS: aPDT is demonstrated by staining S. mutans with PB and irradiating blue light used for resin polymerization and tooth bleaching to generate ROS. Therefore, plaque-disclosing solution-based aPDT against S. mutans might represent a new method for cleaning pit and fissure grooves.

ATML1 activity is restricted to the outermost cells of the embryo through post-transcriptional repressions.

Cell fate determination in plants relies on positional cues. To investigate the position-dependent gene regulation in plants, we focused on shoot epidermal cell specification, which occurs only in the outermost cells. ATML1, which encodes an HD-ZIP class IV transcription factor, is a positive regulator of shoot epidermal cell identity. Despite the presence of a weak ATML1 promoter activity in the inner cells, ATML1 protein was detected mostly in the outermost cells, which suggests that ATML1 accumulation is inhibited in the inner cells. ATML1 nuclear localization was reduced in the epidermis and there was a positive, albeit weak, correlation between the amount of ATML1 in the nuclei and the expression of a direct target of ATML1. Nuclear accumulation of ATML1 was more strongly inhibited in the inner cells than in the outermost cells. Domain deletion analyses revealed that the ZLZ-coding sequence was necessary and partially sufficient for the post-transcriptional repression of ATML1 Our results suggest that post-transcriptional repressions contribute to the restriction of master transcriptional regulator activity in specific cells to enable position-dependent cell differentiation.

Effects of blue-light irradiation during dental treatment.

In dentistry, blue light is widely used for tooth bleaching and restoration procedures involving composite resin. In addition, many dentists use magnification loupes to enable them to provide more accurate dental treatment. Therefore, the use of light is indispensable in dental treatment. However, light can cause various toxicities, and thermal injuries caused by light irradiation are regarded as particularly important. In recent years, the eye damage and non-thermal injuries caused by blue light, the so-called "blue light hazard", have gained attention. Unfortunately, much of the research in this field has just begun, but our recent findings demonstrated that blue-light irradiation generates reactive oxygen species (ROS) and induces oxidative stress in oral tissue. However, they also showed that such oxidative stress is inhibited by antioxidants. There have not been any reports that suggested that the ROS-induced phototoxicity associated with blue-light irradiation causes direct clinical damage, but some disorders are caused by the accumulation of ROS. Therefore, it is presumed that it is necessary to suppress the accumulation of oxidative stressors in oral tissues during treatment. In the future, we have to promote discussion about the suppression of phototoxicity in dentistry, including concerning the use of antioxidants to protect against phototoxic damage.

Assessment of laparoscopic training for gynecological malignancies using Thiel-embalmed human cadavers.

The introduction of laparoscopic surgery has also been beneficial for patients with gynecological malignancies. In this respect, surgeons should receive related training in the context of human resource development. Hands-on training was introduced using Thiel-embalmed human cadavers (THCs) in 2014. To determine the usefulness of THCs, they were evaluated in terms of tissue color, consistency and operative tactility, among others, compared with in vivo laparoscopic training for gynecological malignancies. Hands-on training sessions using THCs were held for a total of 11 times at Ehime University Graduate School of Medicine between March 2014 and October 2017. Training on THCs included advanced laparoscopic procedures for radical hysterectomy type III. At the end of each training session, data were collected using a standardized, anonymous questionnaire termed the Likert scale. THCs ensured flexibility and plasticity of tissues and organs; therefore, the working space was similar to that in the living body under pneumoperitoneum. After analyzing the quality and consistency of tissue and organ color compared with in vivo conditions, most of the participants agreed or strongly agreed regarding the uterus, adnexa and ureter, but not regarding the large blood vessels. The highest scores were observed in the authenticity of the anatomical condition of each organ. Most participants strongly agreed that training using THCs would help improve their laparoscopic skills with a high level of satisfaction. Furthermore, most participants reported that they would recommend this training to other obstetrician-gynecologists. Laparoscopic training for gynecological malignancies using THCs was comparable to the in vivo conditions in terms of surgical view and operative tactility. Therefore, THCs may be an excellent training tool for improving laparoscopic surgical skills for gynecological malignancies.