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In recent years, the health benefits of lactic acid bacteria have garnered attention, but their antioxidant activity remains relatively underexplored. We have been analyzing the antioxidant activities of various dietary phytochemicals by assessing their ability to mitigate oxidative stressor-induced toxicity in zebrafish larvae through pretreatment. In this study, the antioxidant activities of 24 strains of heat-killed lactic acid bacteria from various origins were examined using this zebrafish assay system. The results revealed that all 24 strains possessed antioxidant activity that reduces hydrogen peroxide toxicity. Further detailed analysis using the H61 strain, which exhibited the strongest activity, showed that no direct antioxidant activity was observed in the assay system, suggesting that the detected antioxidant activity was entirely indirect. Moreover, it was found that pretreatment of zebrafish larvae with the H61 strain for more than 6 h was required to exert its antioxidant activity. This duration was similar to that required by dietary antioxidants that activate the Keap1-Nrf2 pathway, suggesting potential involvement of this pathway. However, analysis using Nrf2-knockout zebrafish revealed that the antioxidant activity of strain H61 is independent of Nrf2, indicating that it represents a novel indirect antioxidant activity that does not involve the Keap1-Nrf2 pathway. To further characterize this activity, the ability to mitigate the toxicity of oxidative stressors other than hydrogen peroxide was examined. The results indicated that while the toxicity of tert-butyl hydroperoxide was reduced, unlike with the Keap1-Nrf2 pathway, it was not effective in counteracting the toxicity of paraquat or arsenite, which generate superoxide radicals. In conclusion, we have identified a novel indirect antioxidant activity in lactic acid bacteria.

Purpose In Japan, severe maxillary anterior crowding (MxAC) has historically been considered a positive feature of a girl’s smile, but no comparative studies with other countries have been conducted. Therefore, the present study compared the perceptions of smile attractiveness of adolescent patients with MxAC between the general populations in Japan and the United States using a web-based, questionnaire survey.Materials and methods Smiling frontal facial images of six adolescent patients with severe MxAC photographed before and after treatment were selected. A total of 200 age- and gender-matched participants were selected from the general populations in Japan and the United States as the JP and US groups, respectively. The attractiveness of images was evaluated using a Likert scale, and the number of images positively evaluated among 6 models was calculated as the preference score. Higher preference score indicated more positive attitudes towards those images. The preference scores were compared between the groups, and between before and after orthodontic treatment, as well as between age and gender subgroups for both groups.Results The preference scores were significantly higher before treatment and significantly lower after treatment for the JP group than for the US group. The preference score for before treatment in females was significantly higher in the JP group than the US group. The preference score for after treatment in adults was significantly lower in the JP group than the US group.Conclusions The smiling facial images of adolescent girls with MxAC are more preferred in Japan than in the United States, but this association is reversed after orthodontic treatment.

Abstract Background Epithelioid hemangioendothelioma (EHE) is a rare and slow-growing malignant vascular neoplasm composed of epithelioid endothelial cells within a distinctive myxohyaline stroma. It most commonly involves somatic soft tissue, lungs, liver and bone. Herein, we describe a case of EHE arising in the axillary region. Case presentation A 61-year-old man was under observation for multiple hepatic hemangiomas. Fluorodeoxyglucose–positron emission tomography/computed tomography showed specific uptake in a right axillary tumor. The patient was referred to our department for further investigation of the axillary tumor. An elastic-soft and poorly mobile tumor was palpable in the right axilla. Contrast-enhanced computed tomography showed a right axillary tumor and enlarged hepatic hemangiomas. In addition, multiple nodules in both lungs, a left renal angiomyolipoma, and left adrenal adenoma were revealed. Ultrasonography showed masses in both lobes of the thyroid gland, and a 30-mm lobulated hypoechoic mass in the axilla with well-defined and rough borders, showing internal heterogeneity. Fine-needle aspiration cytology was performed on the thyroid and axillary tumors: the thyroid tumor was class V, raising suspicion of papillary thyroid cancer (PTC); the left superior internal jugular node was class V, raising suspicion of metastasis of PTC; and the axillary tumor was class III, raising suspicion of a mesenchymal tumor with few epithelioid cells. The multiple lung nodules were diagnosed as metastatic tumors derived from thyroid cancer. We diagnosed these diseases as PTC of T1b(m)N1bM1(lung) Stage IVB and a right axillary tumor of unclear origin. However, it was assumed to be a primary mesenchymal tumor or a lymph node metastasis from lung cancer or occult breast cancer. We performed total thyroidectomy, left cervical lymph node dissection, and right axillary tumor excision. Histopathologic examination revealed the thyroid tumor as a PTC and the axillary tumor as an EHE. The EHE showed nuclear atypia, necrosis and high mitotic figures. Hence, it was considered to be a high-risk EHE. Conclusions We experienced a rare primary subcutaneous axillary EHE with metastatic thyroid cancer in the lung. Since our case was classified as a high-risk EHE, a close follow-up would be appropriate.

The Keap1–Nrf2 pathway is an evolutionarily conserved mechanism that protects cells from oxidative stress and electrophiles. Keap1 is a repressor of Nrf2 in normal cellular conditions but also a stress sensor for Nrf2 activation. Interestingly, fish and amphibians have two Keap1s (Keap1a and Keap1b), of which Keap1b is the ortholog of mammalian Keap1. Keap1a, on the other hand, is a gene found only in fish and amphibians, having been lost during the evolution to amniotes. We have previously shown that keap1b-knockout zebrafish have increased Nrf2 activity and reduced response to certain Nrf2-activating compounds but that they grow normally to adulthood. This may be because the remaining keap1a suppresses the hyperactivation of Nrf2, which is responsible for the post-natal lethality of Keap1-knockout mice. In this study, we analyzed keap1a;keap1b-double-knockout zebrafish to test this hypothesis. We found that keap1a;keap1b-double-knockout zebrafish, like Keap1-knockout mice, showed eating defects and were lethal within a week of hatching. Genetic introduction of the Nrf2 mutation rescued both the eating defects and the larval lethality, indicating that Nrf2 hyperactivation is the cause. However, unlike Keap1-knockout mice, keap1a;keap1b-double-knockout zebrafish showed no physical blockage of the food pathway; moreover, the cause of death was not directly related to eating defects. RNA-sequencing analysis revealed that keap1a;keap1b-double-knockout larvae showed extraordinarily high expression of known Nrf2-target genes as well as decreased expression of visual cycle genes. Finally, trigonelline or brusatol partially rescued the lethality of keap1a;keap1b-double-knockout larvae, suggesting that they can serve as an in vivo evaluation system for Nrf2-inhibiting compounds.

The costimulatory signal regulated by the members of the tumor necrosis factor receptor (TNFR) superfamily expressed by T cells plays essential roles for T cell responses and has emerged as a promising target for cancer immunotherapy. However, it is unclear how the difference in TNFR costimulation contributes to T cell responses. In this study, to clarify the functional significance of four different TNFRs, OX40, 4-1BB, CD27 and GITR, we prepared corresponding single-chain TNF ligand proteins (scTNFLs) connected to IgG Fc domain with beneficial characteristics, i.e., Fc−scOX40L, Fc−sc4-1BBL, Fc−scCD27L (CD70) and Fc−scGITRL. Without intentional cross-linking, these soluble Fc−scTNFL proteins bound to corresponding TNFRs induced NF-kB signaling and promoted proliferative and cytokine responses in CD4+ and CD8+ T cells with different dose-dependencies in vitro. Mice injected with one of the Fc−scTNFL proteins displayed significantly augmented delayed-type hypersensitivity responses, showing in vivo activity. The results demonstrate that each individual Fc−scTNFL protein provides a critical costimulatory signal and exhibits quantitatively distinct activity toward T cells. Our findings provide important insights into the TNFR costimulation that would be valuable for investigators conducting basic research in cancer immunology and also have implications for T cell-mediated immune regulation by designer TNFL proteins.

Necrosis, a form of cell death, occurs not only with the development of various diseases but also with a tumor tissue response to cancer treatment. Therefore, pursuing progress for cancer therapy through induction of necrosis may be one of the most effective approaches for cancer eradication. We herein describe the development of a real-time imaging system to visualize intratumoral necrosis. The system is composed of two types of cells expressing either one of two necrosis imaging reporters that consist of a DnaE intein sequence linking to one of two split-luciferase fragments. When necrosis occurs in a tumor composed of both of the cells, the two types of leaked reporters can reconstitute the enzymatic activity as a result of protein trans-splicing and thereby emit bioluminescence in the presence of the substrate. This system, which was constructed with shrimp-derived luciferase, allowed in vitro imaging of necrosis. We further confirmed real-time imaging of intratumoral necrosis caused by physical or chemical tissue disruption, validating its application in in vivo necrosis imaging. Thus, the constructed imaging system could be a powerful tool for the optimization of the therapeutic condition for cancer therapy and for the evaluation of novel anticancer drugs targeting necrosis.

Abstract Background Pulmonary epithelial–myoepithelial carcinoma is a rare subtype of lung cancer. Because of its rarity, the molecular information on this carcinoma is insufficient. Case presentation We report a case of pulmonary epithelial–myoepithelial carcinoma without AKT1, HRAS or PIK3CA mutations in a 76-year-old woman. Computed tomography revealed a tumor located in the left lower lung. Thoracoscopic left lower lobectomy was performed. Histopathologically, the tumor consisted of duct-like structures and polygonal and spindle cell features. The duct-like structures were composed of two distinct cell layers. The inner layer consisted of cuboidal cells that were positive for pan-cytokeratin and negative for p63, whereas the outer layer consisted of polygonal and spindle cells that were positive for p63 and weakly positive for pan-cytokeratin. We evaluated mutations in AKT1, BRAF, CTNNB1, HRAS, KRAS and PIK3CA but did not detect any mutations. Conclusion Pulmonary epithelial–myoepithelial carcinoma is a rare subtype of lung cancer, with only 56 previous cases reported in the English literature. The genetic alterations in pulmonary epithelial–myoepithelial carcinoma are still unknown. We examined the 6 genes mutation analysis, however no mutation was detected.

Abstract Background Locomotive syndrome (LoS) is defined as the loss of mobility due to age-related impairment of motor organs. The purpose of this study was to evaluate the prevalence and severity of LoS, muscular strength and balancing ability, and prevalence of sarcopenia in relation to the presence of LoS according to sex and age groups ranging between 50 and 89 years. Methods Male and female participants between the ages of 50–89 were randomly selected in the resident registry of a cooperating town. Calls for participation continued until approximately 50 consenting participants were successfully recruited for each age group and sex. A total of 413 participants (203 male and 210 female) were enrolled for undergoing a LoS risk test and measuring their physical function. Physical function was compared to participants with or without LoS. Results A total of 312 patients (75.5%) were diagnosed as LoS, of which 144 (46.2%) were male and 168 (53.8%) were female. The severity of LoS for the 312 patients were 210 (67.3%) for stage 1 and 102 (32.7%) for stage 2. The prevalence of LoS in males were 37, 59, 91, and 100% in the 50s, 60s, 70s, and 80s age strata, respectively. The prevalence of LoS in females were 71, 62, 89, and 98% in the 50s, 60s, 70s, and 80s age strata, respectively. The prevalence of sarcopenia was significantly higher as the age strata in males grew higher. Knee extension strength was significantly lower for participants in their 50s and females in addition to females in their 60s with LoS. The 31 patients diagnosed as sarcopenia included 29 (93.5%) with LoS, 11 (35.4%) classified as LoS stage 1, and 18 (58.1%) classified as stage 2. Conclusions The prevalence of LoS was high in participants over 70 years of age. In males, the prevalence of sarcopenia was higher as the age strata grew higher. Patients with LoS exhibited lower knee extension strength. We believe that some measures to prevent or improve LoS may require exercise to increase the muscle strength of the lower limbs.

Summary: Brain development is a highly orchestrated process requiring spatiotemporally regulated mitochondrial dynamics. Drp1, a key molecule in the mitochondrial fission machinery, undergoes various post-translational modifications including conjugation to the small ubiquitin-like modifier (SUMO). However, the functional significance of SUMOylation/deSUMOylation on Drp1 remains controversial. SUMO-specific protease 5 (Senp5L) catalyzes the deSUMOylation of Drp1. We revealed that a splicing variant of Senp5L, Senp5S, which lacks peptidase activity, prevents deSUMOylation of Drp1 by competing against other Senps. The altered SUMOylation level of Drp1 induced by Senp5L/5S affects mitochondrial morphology probably through controlling Drp1 ubiquitination and tubulation of the endoplasmic reticulum. A dynamic SUMOylation/deSUMOylation balance controls neuronal polarization and migration during the development of the cerebral cortex. These findings suggest a novel role of post-translational modification, in which deSUMOylation enzyme isoforms competitively regulate mitochondrial dynamics via Drp1 SUMOylation levels, in a tightly controlled process of neuronal differentiation and corticogenesis.

Abstract Background Angiosarcoma of the breast is rare. It carries a poor prognosis because of its high risk of local recurrence and distant metastases. Presently, there are still no established systemic therapies. Thus, the main treatment strategy for breast angiosarcoma is complete resection. This underscores the importance of closely monitoring the spread of the tumor lesion, particularly for multifocal angiosarcoma, and to plan an optimal operative procedure. We herein present the successful surgical treatment of a rare case of multifocal primary breast angiosarcoma. Case presentation A 43-year-old woman visited our hospital with a growing lump on her right breast accompanied by pain. Clinical and radiological examinations revealed a well-circumscribed 40-mm-diameter tumor at the inner lower quadrant of her right breast. Histological examination of a needle biopsy specimen revealed angiosarcoma. Based on a precise evaluation of the tumor by contrast-enhanced MRI and contrast-enhanced CT scan, a wide local excision with sufficient margins was performed. In the resected specimen, three discontinuous small lesions of angiosarcoma were observed around the main tumor. Therefore, total mastectomy was additionally performed. Pathological examination revealed two other small nodules of angiosarcoma in the remnant right breast, which appeared to be close but not continuous to the defective part of the initial resection. Postoperative follow-up at 1 year showed no signs of recurrence or distant metastasis. Multifocal primary breast angiosarcoma is extremely rare with only two previous reports describing its multifocality. Conclusions Owing to its rarity, a standardized surgical treatment for breast angiosarcoma remains controversial. Our case suggests that primary breast angiosarcoma may occasionally present with multifocal tumor. Thus, it is important to keep in mind the multifocality of breast angiosarcoma when assessing its spread by diagnostic imaging and when planning the surgical strategy.

Abstract Background This study aimed to evaluate the impact of previous local treatment on lymphatic drainage patterns in ipsilateral breast tumor recurrence (IBTR) based on our data on re-operative sentinel lymph node biopsy (re-SLNB) for IBTR. Methods Between April 2005 and December 2016, re-SLNB using lymphoscintigraphy with Tc-99 m phytate was performed in 136 patients with cN0 IBTR. Patients were categorized into two groups: the AX group included 55 patients with previous axillary lymph node dissection; the non-AX group included 69 patients with previous SLNB and 12 patients with no axillary surgery. The whole breast irradiation (RT) after initial surgery had performed in 17 patients in the AX group and 27 patients in the non-AX group. Results Lymphatic drainage was visualized in 80% of the AX group and 95% of the non-AX group (P

Summary: Engagement of neural stem/progenitor cells (NSPCs) into proper neuronal differentiation requires the spatiotemporally regulated generation of metabolites. Purines are essential building blocks for many signaling molecules. Enzymes that catalyze de novo purine synthesis are assembled as a huge multienzyme complex called “purinosome.” However, there is no evidence of the formation or physiological function of the purinosome in the brain. Here, we showed that a signal transduction ATPases with numerous domains (STAND) protein, NACHT and WD repeat domain-containing 1 (Nwd1), interacted with Paics, a purine-synthesizing enzyme, to regulate purinosome assembly in NSPCs. Altered Nwd1 expression affected purinosome formation and induced the mitotic exit and premature differentiation of NSPCs, repressing neuronal migration and periventricular heterotopia. Overexpression/knockdown of Paics or Fgams, other purinosome enzymes, in the developing brain resulted in a phenocopy of Nwd1 defects. These findings indicate that strict regulation of purinosome assembly/disassembly is crucial for maintaining NSPCs and corticogenesis.

Recent studies demonstrated that insulin signaling plays important roles in the regulation of pancreatic β cell mass, the reduction of which is known to be involved in the development of diabetes. However, the mechanism underlying the alteration of insulin signaling in pancreatic β cells remains unclear. The involvement of epigenetic control in the onset of diabetes has also been reported. Thus, we analyzed the epigenetic control of insulin receptor substrate 2 (IRS2) expression in the MIN6 mouse insulinoma cell line. We found concomitant IRS2 up-regulation and enhanced insulin signaling in MIN6 cells, which resulted in an increase in cell proliferation. The H3K9 acetylation status of the Irs2 promoter was positively associated with IRS2 expression. Treatment of MIN6 cells with histone deacetylase inhibitors led to increased IRS2 expression, but this occurred in concert with low insulin signaling. We observed increased IRS2 lysine acetylation as a consequence of histone deacetylase inhibition, a modification that was coupled with a decrease in IRS2 tyrosine phosphorylation. These results suggest that insulin signaling in pancreatic β cells is regulated by histone deacetylases through two novel pathways affecting IRS2: the epigenetic control of IRS2 expression by H3K9 promoter acetylation, and the regulation of IRS2 activity through protein modification. The identification of the histone deacetylase isoform(s) involved in these mechanisms would be a valuable approach for the treatment of type 2 diabetes.

Facile detection and the identification of hazardous organic solvents are essential for ensuring global safety and avoiding harm to the environment caused by industrial wastes. Here, we present a simple method for the fabrication of silver-coated monodisperse polystyrene nanoparticle photonic structures that are embedded into a polydimethylsiloxane (PDMS) matrix. These hybrid materials exhibit a strong green iridescence with a reflectance peak at 550 nm that originates from the close-packed arrangement of the nanoparticles. This reflectance peak measured under Wulff-Bragg conditions displays a 20 to 50 nm red shift when the photonic sensors are exposed to five commonly employed and highly hazardous organic solvents. These red-shifts correlate well with PDMS swelling ratios using the various solvents, which suggests that the observable color variations result from an increase in the photonic crystal lattice parameter with a similar mechanism to the color modulation of the chameleon skin. Dynamic reflectance measurements enable the possibility of clearly identifying each of the tested solvents. Furthermore, as small amounts of hazardous solvents such as tetrahydrofuran can be detected even when mixed with water, the nanostructured solvent sensors we introduce here could have a major impact on global safety measures as innovative photonic technology for easily visualizing and identifying the presence of contaminants in water.

Effects of electrolytes on bubble coalescence are investigated experimentally from fluid dynamic point of view. Collisions of a bubble with free surface in two kinds of liquids, namely, ultrapure water and sodium chloride solution, are observed using a high speed camera. It is found that the repetitive number of bubble bounces on a free surface in electrolyte solution is larger than that in ultrapure water when the equivalent bubble radii are the same. This result qualitatively shows that electrolyte works to prevent bubbles from coalescing. It is also revealed that the bubbles can coalesce if their Weber numbers, which are based on the radius of curvature of the front side of the bubble and the approach velocity just before the collision with the free surface, are less than a critical Weber number. Furthermore, the critical Weber number decreases with the increase in the concentration of the electrolyte solutions despite the fluid dynamic characteristics, such as bubble rise velocity and bubble shape, are not affected by the addition of the electrolytes. It is concluded that Weber number is the most important parameter to specify the effects of electrolytes on bubble coalescence.

Bamboos are typical examples of highly synchronized semelparous species. Their mass-flowering events occur at supra-annual intervals but they sometimes flower on a small scale in off-years. If some bamboo ramets (culms) of a genet flower and die in off-years, whereas other culms of the same genet do not flower synchronously, the genet can still survive blooming in an off-year and could participate in the next mass-flowering event. At genet level, the effect might be similar to that achieved by synchronously reproducing iteroparous plants. In addition, if multiple genets flower simultaneously in off-years, cross-pollination will be promoted. However, it is not known whether all the culms in a genet flower synchronously and whether multiple genets flower in off-years. We determined the clonal structure of three temperate dwarf bamboo species, i.e., Sasa senanensis, S. kurilensis, and S. palmata, at 24 off-year flowering sites and the surrounding areas in northern Japan using seven microsatellite markers. We also estimated seed set at seven of the sites and self-pollination rates at five sites to determine off-year reproductive success. Next, we investigated whether seed sets at the culm level were related to flowering area and/or number of flowering genets, using generalized linear mixed-effect models (GLMMs). Multiple genets flowered at 9/24 flowering sites. We found that 40/96 of the genets identified had some flowering culms. Non-flowering culms were present in 24/40 flowering genets. Seed set was in the range 2.2%-12.5% and the self-pollination rate was 96.3%. In the best GLMM, seed set increased with flowering area. Seeds were produced in off-years, but cross-pollination was rare in off-years. We suggest that some dwarf bamboos may exhibit iteroparity or imperfectly synchronized semelparity at the genet level, a characteristic similar to that of other reproductively synchronous plants. We also found synchronous flowering of a few genets even in off-years.

Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms. Male C57BL/6J mice (10 wk old) were randomly assigned to one of the three experimental groups: nonimmobilization control group (sterilized water injection), immobilization control group (sterilized water injection), and immobilization and MOTS-c-treated group (15 mg/kg/day MOTS-c injection). We used casting tape for the immobilization experiment. After 8 days of the experimental period, skeletal muscle samples were collected and used for Western blotting, RNA sequencing, and lipid and collagen assays. Immobilization reduced ~15% of muscle mass, whereas MOTS-c treatment attenuated muscle loss, with only a 5% reduction. MOTS-c treatment also normalized phospho- AKT, phospho-FOXO1, and phospho-FOXO3a expression levels and reduced circulating inflammatory cytokines, such as interleukin-1b (IL-1b), interleukin-6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1), in immobilized mice. Unbiased RNA sequencing and its downstream analyses demonstrated that MOTS-c modified adipogenesis- modulating gene expression within the peroxisome proliferator-activated receptor (PPAR) pathway. Supporting this observation, muscle fatty acid levels were lower in the MOTS-c-treated group than in the casted control mice. These results suggest that MOTS-c treatment inhibits skeletal muscle lipid infiltration by regulating adipogenesis-related genes and prevents immobilization- induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of several etching products prior to the application of a one-step self-etch adhesive (1-SEA) or two-step self-etch adhesive (2-SEA) on enamel by microshear bond strength (μSBS) testing and observation of the adhesive-enamel interface. Materials and Methods: Ground human enamel surfaces were randomly assigned to one of eight groups according to the combination of surface treatments (either no conditioner [NC], ME [Multi Etchant], EC [Enamel Conditioner], or KE [K-etchant Gel]) and adhesive (ADU [Adhese Universal] or SE2 [Clearfil SE Bond 2]). All groups were further divided into two subgroups: 0 or 10,000 thermal cycles (TC). Then, the μSBS test was performed. The adhesive-enamel interface after acid-base challenge and the surface structure after conditioner application were also observed. Results: With 10,000 TCs, there was no statistically significant difference between ME-ADU and NC-ADU. On the other hand, the μSBS of EC-ADU or KE-ADU was significantly higher than that of NC-ADU, while that of ME-SE2 was significantly lower than NC-SE2. There was no significant difference between EC-SE2, NC-SE2, and KE-SE2. Formation of an acid-base resistance zone (ABRZ) was confirmed in all groups. However, funnel-shaped erosion, which indicates interfacial defects, was observed in the NC-ADU, ME-ADU, and ME-SE2 groups. Conclusion: For enamel bonding, application of EC or KE prior to ADU increased the bond strength and created a stable adhesive-enamel interface. On the other hand, SE2 also had stable shear bond strength and interface without the use of conditioners. However, ME decreased the bonding performance of SE2. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of pre-etching for two-step self-etch adhesive bonding to bur-cut and uncut enamel. Burcut and uncut enamel surfaces were assigned to surface treatments of no etchant (CT), Enamel Conditioner (EC; Shofu, Kyoto, Japan), or K-etchant syringe (KE; Kuraray Noritake Dental, Tokyo, Japan). The bonded samples were thermal cycled and evaluated by microshear bond strength (µSBS). The adhesive interface after acid-base challenge and the conditioned enamel surfaces were morphologically analyzed using scanning electron microscopy (SEM). For bur-cut enamel, EC and KE pre-etching significantly improved µSBS. For uncut enamel, KE showed higher µSBS than EC. SEM observation revealed that only KE removed the prismless layer of the uncut enamel surface. EC could improve enamel bonding and appears to be a substitute for phosphoric acid, especially for bur-cut enamel. However, uncut enamel could not be effectively conditioned by EC with a lower bond strength than KE. [ABSTRACT FROM AUTHOR]

Abstract Background An aortoesophageal fistula can prove to be fatal. Salvage thoracic endovascular aortic repair as a bridging therapy and radical surgery with thoracotomy should be considered while treating aortoesophageal fistula without spontaneous closure. Moreover, it is essential to select a technique that reduces the risk of reinfection. Here we report a rare case of a ruptured thoracic aortic aneurysm related to esophageal perforation by a fish bone that led to massive hematemesis and shock, and the surgical treatment of an aortoesophageal fistula that developed after salvage thoracic endovascular aortic repair. Case presentation A 70-year-old Japanese female patient was admitted with hematemesis, thoracic pain, and shock related to esophageal perforation of a ruptured descending aortic aneurysm caused by fish bone aspiration and esophageal perforation 1 month previously. An emergency thoracic endovascular aortic repair was performed. Postoperatively, an aortoesophageal fistula that remained open and a food intake-related increase in the inflammatory response was noted. Radical blood-vessel prosthesis implantation and fistula closure were performed. The patient’s postoperative course was favorable and the patient was discharged 22 days after the blood vessel prosthesis implantation. Conclusion Such a case of rupture of a descending aortic aneurysm related to perforation by a fish bone and an aortoesophageal fistula is considerably rare. Thus, we report the therapeutic strategy of this particular case and review the relevant literature.

Background/Aim: The prognosis of a cancer patient is influenced by the tumor-related factors, as well as by various patient-related factors. We evaluated the association between inflammatory and nutritional factors and their outcomes, including the prognosis and therapeutic course, in patients with metastatic breast cancer. Patients and Methods: In this observational retrospective study, we evaluated 35 patients. The inflammatory and nutritional markers before systemic therapy included the lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), monocyte-tolymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), pan-immuno-inflammatory values (PIV), prognostic nutritional index (PNI), Glasgow prognostic score (GPS), and psoas muscle index (PMI). Results: Triple-negative, low PNI, and GPS 2 were correlated with worse overall survival in the univariable analysis. The GPS was the only independent predictor of overall survival [hazard ratio=5.85, 95% confidence interval=1.15-29.68, p<0.01]. The time to treatment failure of first-line therapy in patients with GPS 2 was significantly shorter than that in patients with GPS 0/1 (p<0.01). Conclusion: The GPS was an independent predictive marker for overall survival in patients with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

In this study, the influence of primer contamination on enamel bonding was analyzed. Adper Scotchbond Multi-Purpose (SMP), CLEARFIL SE Bond 2 (SE2), Scotchbond Universal (SBU) Adhesive, and Scotchbond Etchant (35% phosphoric acid; PA) were used. Ground bovine enamels were divided into eight groups based on the bonding protocols. The bonding interfaces after an acid–base challenge were observed via scanning electron microscopy to determine the acid–base resistant zone (ABRZ). Moreover, the bonding interfaces after the nanoleakage challenge were analyzed via energy-dispersive X-ray spectroscopy. ABRZ was observed in all the samples except PA_ONLY (applied PA etching, No primer and No adhesive resin). The funnel-shaped erosion was detected only in X_SBU (applied SBU without PA etching). The nanoleakage test revealed silver patterns in some groups. The nanoleakage, i.e., the penetration of the silver ions, was detected in the groups wherein primer was applied on PA–pre-etched enamel. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of temporary sealing materials and cleaning protocols on the bond strength of resin cement applied to dentin using resin-coating technique. Scotchbond Universal Adhesive and Filtek Supreme Ultra Flowable were applied to bovine dentin. Forty-five specimens were divided into the following three groups according to the temporary sealing materials: Cav-: CAVITON EX, Vas-: COCOA BUTTER and FIT SEAL, and Sep-: Washable SEP and FIT SEAL. Each material was placed on resin- coated dentin. After 1-week water storage, one of the following three cleaning protocols was performed: -WA: washed with water, -BR: brushed with PRESSAGE, and -AF: cleaned with AIR-FLOW. Microtensile bond strength test and EDS analysis were conducted. Irrespective of the cleaning protocol used, Washable SEP demonstrated less residual debris on resin-coated dentin, resulting in high bond strength. Regardless of the temporary sealing material applied, AIR-FLOW demonstrated less residual debris, resulting in high bond strength. [ABSTRACT FROM AUTHOR]

Objective: Unusual setting of medical care Background: Extrahepatic portal vein obstruction (EHPVO) is one of the most important diseases that causes pre-hepatic portal hypertension, and EHPVO sometimes develops cavernous transformation to maintain hepatopetal flow. In this report, we describe the first case of hepatocellular carcinoma (HCC) with EHPVO having underwent pure laparoscopic left hepatectomy with middle hepatic vein (MHV) resection. Case Report: A 70-year-old woman with a diagnosis of mixed-type HCC or cholangiocarcinoma located in segment 4b was referred to our hospital, and computed tomography revealed EHPVO with cavernous transformation. We successfully performed pure laparoscopic left hepatectomy with MHV resection by using the individual hilar approach, frequent intraoperative sonography, and indocyanine green imaging. In this case, the routine Glissonian approach was impossible due to cavernous transformation growth and the absence of a portal vein. Therefore, frequent confirmation of intrahepatic flow was crucial to avoid intraoperative complications. The patient was discharged with no complications on postoperative day 7. A histopathological examination revealed that the moderately differentiated HCC formed a pseudoglandular pattern and cord-like structures, thereby defined as type II according to Edmondson's classification. Conclusions: Currently, difficulty scoring systems for laparoscopic liver resection (LLR) usually contain the procedure and location of the hepatic tumor, but they do not contain the variety of anatomical abnormality due to its rarity. However, the false recognition of hilar vessels and biliary ducts in patients with an anatomical abnormality, including EHPVO, leads to severe injury; therefore, anatomical variety and abnormality are also important factors increasing the difficulty of LLR. [ABSTRACT FROM AUTHOR]

Background: Kommerell's diverticulum with Stanford type A aortic dissection is a relatively rare condition. There is currently no standard treatment strategy for Kommerell's diverticulum. We herein report our surgical strategy with a review of literature for a case of Kommerell's diverticulum that developed acute aortic dissection. Case presentation: A 54-year-old woman was referred to our hospital after being diagnosed with Stanford type A acute aortic dissection at the hospital where she was admitted for chest and back pain. Contrast-enhanced computed tomography showed a right and left common carotid and left subclavian artery branching from the aortic arch; Kommerell's diverticulum and an aberrant right subclavian artery (RSCA) arising from it were noted in the distal arch. The contralateral aortic wall where Kommerell's diverticulum was located was the entry, resulting in aortic dissection, with retrograde dissection extending into the ascending aorta. Partial thrombosis was detected in the false lumen of the ascending aorta. The dissection extended from the ascending aorta to the common iliac artery. In addition, the thrombosed false lumen in the left common iliac artery was considered to have caused dynamic obstruction due to compression and narrowing of the true lumen. Based on these findings, total arch replacement with reconstruction of the 4-branched vessels in the arch, including an aberrant RSCA, the frozen elephant trunk technique, and femoro-femoral bypass for malperfusion of the left lower extremity were performed with deep hypothermic circulatory arrest. An artificial graft was anastomosed to the right axillary artery, which was used as the blood supply route for cardiopulmonary bypass. After cooling to hypothermia, the central portion of the aberrant right subclavian artery was clipped on the right side of the trachea. Thus, cerebral blood flow was maintained via the right vertebral artery, the aortic arch was opened, and cannulas for selective cerebral perfusion were inserted into the right common carotid artery, the left common carotid artery, and the left subclavian artery. After each vessel was reconstructed, the graft that had been anastomosed to the right axillary artery was anastomosed to the graft used for reconstruction of the right common carotid artery. The patient's postoperative course was generally good. Conclusion: The strategy used by us effectively created transient occlusion of the origin of Kommerell's diverticulum and the primary entry. Our results indicate that this method is feasible and effective for cases in which in situ reconstruction of the branch may be challenging.

Cancer stem-like cells (CSCs) are expanded in the CSC niche by increased frequency of symmetric cell divisions at the expense of asymmetric cell divisions. The symmetric division of CSCs is important for the malignant properties of cancer; however, underlying molecular mechanisms remain largely elusive. Here, we show a cytokine, semaphorin 3 (Sema3), produced from the CSC niche, induces symmetric divisions of CSCs to expand the CSC population. Our findings indicate that stimulation with Sema3 induced sphere formation in breast cancer cells through neuropilin 1 (NP1) receptor that was specifically expressed in breast CSCs (BCSCs). Knockdown of MICAL3, a cytoplasmic Sema3 signal transducer, greatly decreased tumor sphere formation and tumor-initiating activity. Mechanistically, Sema3 induced interaction among MICAL3, collapsin response mediator protein 2 (CRMP2), and Numb. It appears that activity of MICAL3 monooxygenase (MO) stimulated by Sema3 is required for tumor sphere formation, interaction between CRMP2 and Numb, and accumulation of Numb protein. We found that knockdown of CRMP2 or Numb significantly decreased tumor sphere formation. Moreover, MICAL3 knockdown significantly decreased Sema3-induced symmetric divisions in NP1/Numb-positive BCSCs and increased asymmetric division that produces NP1/Numb negative cells without stem-like properties. In addition, breast cancer patients with NP1-positive cancer tissues show poor prognosis. Therefore, the niche factor Sema3-stimulated NP1/MICAL3/CRMP2/Numb axis appears to expand CSCs at least partly through increased frequency of MICAL3-mediated symmetric division of CSCs. [ABSTRACT FROM AUTHOR]

Endometriosis is characterized by the presence of inflamed and fibrotic endometrial tissue outside the uterine cavity. Previously, we found decreased SERPINA1 (alpha-1 antitrypsin) expression in endometriosis-like lesions in a mouse model of endometriosis, suggesting that it exacerbated inflammation in these lesions. However, the molecular mechanism(s) by which SERPINA1 affects expression of inflammatory factors and development of endometriotic lesions have not been fully characterized. To investigate the role of intracellular SERPINA1 in endometrial stromal cells (ESCs), we performed RNA sequence analysis using RNA extracted from ESCs in which SERPINA1 was knocked down. The analysis identified several toll-like receptor (TLR)-related factors as being upregulated. Silencing of SERPINA1 increased expression of TLR3 and TLR4 in ESCs, as well as several TLR signaling pathway components, including MYD88, IRAK1/4, interleukin (IL)-1β, and interferon (IFN)-β. TLR3 or TLR4 agonists increased expression of inflammatory factors in SERPINA1-knockdown ESCs, whereas TLR3 or TLR4 inhibitors decreased expression. In addition, treatment with recombinant IL-1β or IFN-β increased expression of MYD88 and inflammatory factors in ESCs. Immunohistochemical analysis of endometriotic tissues showed that TLR3, TLR4, and MYD88 were localized in endometriosis lesions. Taken together, the data suggest that reduced expression of SERPINA1 induces expression of inflammatory factors by ESCs, which in turn are associated with TLR3/4, IL-1β, and IFN-β signaling. Regulation of intracellular SERPINA1 levels in ESCs may be a strategy to inhibit inflammatory responses in endometriotic lesions.

T-cell leukemia (ATL) is an intractable blood cancer caused by the infection of human T-cell leukemia virus type-1, and effective medical treatment is required. It is known that the structure and expression levels of cell surface sugar chains vary depending on cell states such as inflammation and cancer. Thus, it is expected that the antibody specific for ATL cell surface sugar chain would be an effective diagnostic tool and a strong candidate for the development of an anti- ATL drug. Here, we developed a stable sugar chainbinding single-chain variable fragment antibody (scFv) that can bind to ATL cells using a fibre-type Sugar Chip and phage display method. The fiber-type Sugar Chips were prepared using O-glycans released from ATL cell lines. The scFv-displaying phages derived from human B cells (diversity: 1.04x108) were then screened using the fiber-type Sugar Chips, and an Oglycan- binding scFv was obtained. The flow cytometry analysis revealed that the scFv predominantly bound to ATL cell lines. The sugar chain-binding properties of the scFv was evaluated by array-type Sugar Chip immobilized with a library of synthetic glycosaminoglycan disaccharide structures. Highly sulphated disaccharide structures were found to have high affinity to scFv. [ABSTRACT FROM AUTHOR]

Abstract In patients with a narrow sinotubular junction, small sinus of Valsalva, or extensibility loss in the aortic root, aortic valve replacement (AVR) with a standard valve is challenging due to limited surgical field. Detailed preoperative measurements of the aortic root render performing AVR using the Perceval valve easy.

The article presents a case study of a 60-year-old female patient with recurrent cystitis wherein cystoscopy found a mass lesion in the urinary bladder.

Abstract Background Immunotactoid glomerulopathy (ITG) is a rare glomerulonephritis characterized by microtubular deposits. Immunofluorescence findings are necessary to differentiate ITG from other proliferative glomerular diseases. The characteristic tubular structure on electron microscopy is essential for a definitive diagnosis, and the diameter of the structure has been traditionally used for differentiating between ITG and other types of glomerulonephritis with organized deposits. In recent years, the disease concept of monoclonal gammopathy of renal significance, which is associated with M protein produced by plasma cell tumors, has been proposed. Case presentation This was a peculiar case of ITG with underlying monoclonal gammopathy in which IgG showed a false-negative result with immunofluorescence using frozen sections. Additional examinations using a different clone of the anti-IgG antibody revealed typical IgG staining. C4d was strongly positive, consistent with immune complex type glomerulonephritis. Conclusions This case highlights unusual features of ITG, and provides a practical hint to avoid a diagnostic pitfall.

Abstract Background Complement component 3 (C3) glomerulopathy, which includes dense deposit disease (DDD) and C3 glomerulonephritis, is caused by dysregulation of the alternative complement pathway. In most cases, C3 glomerulopathy manifests pathologically with membranoproliferative glomerulonephritis-like features. An association between C3 glomerulopathy and monoclonal gammopathy was recently reported in several cases, raising the possibility that C3 glomerulopathy is the underlying pathological process in monoclonal gammopathy of renal significance. Case presentation We herein report a case of monoclonal gammopathy-induced DDD that improved histologically and clinically with chemotherapy including bortezomib. Our case is the first in which treatment response can be linked to the histological response. Potential pathological insights are also discussed. Conclusions Rapid and efficient chemotherapy has the potential to limit renal damage in monoclonal gammopathy-associated DDD.

Global warming has caused devastating damage to starch biosynthesis, which has led to the increase in chalky grains of rice. This study was conducted to characterize the qualities of chalky rice grains and to develop the estimation formulae for their quality damage degree. We evaluated the chalkiness of 40 Japonica rice samples harvested in 2019, in Japan. Seven samples with a high ratio of chalky rice grains were selected and divided into two groups (whole grain and chalky grain). As a results of the various physicochemical measurements, it was shown that the surface layer hardness (H1) of cooked rice grains from chalky grains was significantly lower, and their overall hardness was significantly lower than those from the whole grains. In addition, α- and β-amylase activities, and sugar contents of the chalky rice grains were significantly higher than those of the whole rice grains. The developed estimation formula for the degree of retrogradation of H1 based on the α-amylase activities and pasting properties, showed correlation coefficients of 0.84 and 0.81 in the calibration and validation tests, respectively. This result presents the formula that could be used to estimate and to characterize the cooking properties of the rice samples ripened under high temperature.