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Introduction of the robotic stapler has allowed robotic lobectomy to be performed from a surgical console in complete autonomy. The robotic stapler fits a 12-mm port, which is larger than the standard 8-mm port and increases the risk of postoperative pain. However, in many cases, to cover all possible angles of approach, two 12-mm ports are preferably used. However, limiting instrument inventory and simplifying surgical procedures are also desirable to reduce costs. In a multicenter study, we assessed the feasibility of robotic lobectomy with a single type of robotic stapler [SureForm45 Curved-Tip (SF45C); Intuitive Surgical Inc.] inserted through one 12-mm port placed at the anterior tip of the lower intercostal space. We also investigated the potential cost savings of using an additional 60-mm stapler for interlobar division. A total of 135 lobectomy cases were enrolled. In all cases, all stapling procedures were completed using the SF45C inserted from the designated 12-mm port. We found that it was potentially less expensive to use the SureForm60 stapler if more than six SF45C reloads were needed for interlobar division. However, in our series, only 1 case (0.7%) met this requirement. The use of a single type of stapler from one 12-mm port in a robotic lobectomy is technically feasible. This approach may be expected to allow for surgical simplification, minimize the risk of postoperative pain, and reduce inventory costs.
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We studied δ13C, δ15N and δ18O values, and total mercury (THg) concentrations in muscle samples from deep-sea predators - five beaked whale species and sperm whales - stranded along the coast of Hokkaido, in the north of Japan in 2010 and 2019. The δ13C, δ15N and δ18O values, THg concentrations, and body length (BL) of Stejneger's beaked whales were similar to those of Hubbs' beaked whales, which belong to the same genus. In contrast, δ13C values, THg concentrations, and BL of Sato's beaked whales were markedly different from those of Baird's beaked whales, which belong to the same genus. Stejneger's and Hubbs' beaked whales living around Hokkaido may compete in their ecological niches, whereas Sato's and Baird's beaked whales may segregate their ecological niches. Although Cuvier's beaked whales and sperm whales belong to different genera and their BLs were significantly different, their δ13C and δ15N values were similar, probably because they can dive and stay in deeper waters than other beaked whale species. The δ13C values in combined samples from all whales increased with increasing BL, probably owing to the larger whale species' dietary preference for squid. The δ13C values in combined samples from all whales were positively correlated with THg concentrations, whereas the δ15N values in the combined samples were negatively correlated. The δ18O values in combined samples from most whales tended to be positively correlated with THg concentrations. These correlations may be explained by a higher THg load from deep-sea feeding than from pelagic feeding and by a feeding shift towards lower trophic levels.
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Isótopos de Carbono , Mercurio , Isótopos de Nitrógeno , Isótopos de Oxígeno , Cachalote , Ballenas , Animales , Mercurio/análisis , Japón , Isótopos de Nitrógeno/análisis , Isótopos de Carbono/análisis , Ballenas/metabolismo , Isótopos de Oxígeno/análisis , Músculos/química , Contaminantes Químicos del Agua/análisis , Monitoreo del AmbienteRESUMEN
In amniote limbs, Fibroblast Growth Factor 10 (FGF10) is essential for limb development, but whether this function is broadly conserved in tetrapods and/or involved in adult limb regeneration remains unknown. To tackle this question, we established Fgf10 mutant lines in the newt Pleurodeles waltl which has amazing regenerative ability. While Fgf10 mutant forelimbs develop normally, the hindlimbs fail to develop and downregulate FGF target genes. Despite these developmental defects, Fgf10 mutants were able to regenerate normal hindlimbs rather than recapitulating the embryonic phenotype. Together, our results demonstrate an important role for FGF10 in hindlimb formation, but little or no function in regeneration, suggesting that different mechanisms operate during limb regeneration versus development.
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Factor 10 de Crecimiento de Fibroblastos , Animales , Factor 10 de Crecimiento de Fibroblastos/genética , Factor 10 de Crecimiento de Fibroblastos/metabolismo , Miembro Posterior/crecimiento & desarrollo , Regeneración , Pleurodeles/genética , Pleurodeles/crecimiento & desarrollo , Pleurodeles/metabolismoRESUMEN
Strandings of striped dolphins (SD) and short-finned pilot whales (PW) in Hokkaido, northern Japan, are rare but have recently increased, probably due to global warming. We quantified δ13C, δ15N, and δ18O in muscles of SD (n = 7) and PW (n = 3) stranded in Hokkaido and compared these values with those in muscles (red meat products) of hunted SD and PW in three areas of central and southern Japan. δ18O in stranded SD, except for the calf, decreased with increasing body length (BL), whereas δ13C increased, with no BL-related changes in δ15N. The variability of δ18O (range of maximum and minimum) was larger in the stranded SD (7.5 ) than of the hunted SD in three areas (0.9, 1.9, and 1.4 ), whereas that of δ15N was smaller in the stranded SD than in the hunted SD. Similarly, the variability of δ18O was larger in the stranded PW in Hokkaido (3.3 ) than in the hunted PW in central Japan (1.4 ). The larger variability of δ18O and smaller variability of δ15N in stranded SD imply long-term sojourning in coastal waters and feeding on small amounts of limited prey species at low trophic levels before death.
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Ballena de Aleta , Stenella , Calderón , Animales , Isótopos de Oxígeno , Carbono , Nitrógeno , Oxígeno , JapónRESUMEN
Human exposure to persistent organic pollutants (POPs) is reflected by POP concentrations in breast milk. Many studies of POPs in breast milk have been performed in Japan, but insufficient information is available about some legacy POPs (e.g., mirex and toxaphenes, included in the Stockholm Convention in 2001) and novel POPs (e.g., dicofol and endosulfans, included in the Stockholm Convention in 2019 and 2011, respectively). In this study, dicofol, endosulfan, mirex, and toxaphene concentrations in breast milk from 10 prefectures in Japan were determined. The samples were collected between 2005 and 2010, before Stockholm Convention restrictions on endosulfans and mirex were implemented. Common POPs (e.g., polychlorinated biphenyls) were also analyzed to allow the contamination statuses to be compared. The α-endosulfan and ß-endosulfan concentrations were 0.26-13 and 0.012-0.82 ng/g lipid, respectively. The toxaphene #26 and #50 concentrations were <0.08-5.6 and < 0.1-8.5 ng/g lipid, respectively. The dicofol concentrations were <0.01-4.8 ng/g lipid. The mirex concentrations were <0.2-3.5 ng/g lipid. The α- and ß-endosulfan concentrations on a lipid weight basis negatively correlated with the lipid contents of the milk samples (ρ = -0.65, p < 0.01 for α-endosulfan; ρ = -0.58, p < 0.01 for ß-endosulfan). The toxaphene concentrations positively correlated with the lipid contents. The mirex concentrations positively correlated with the maternal age but negatively correlated with the maternal body mass index. No correlations between the dicofol concentrations and the factors were found. Principal component analysis divided the data into four groups, (1) chlordanes, dichlorodiphenyltrichloroethanes and related compounds, hexachlorobenzene, hexachlorocyclohexanes, hexachloroethane, and polychlorinated biphenyls, (2) endosulfans, (3) dicofol, dieldrin, and toxaphenes, and (4) bromodiphenyl ether 47. This indicated that bromodiphenyl ether 47, dicofol, endosulfans, and toxaphenes have different exposure routes or different kinetics to the other legacy POPs.
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Contaminantes Ambientales , Bifenilos Policlorados , Toxafeno , Femenino , Humanos , Dicofol/análisis , Endosulfano/análisis , Mírex/análisis , Leche Humana/química , Bifenilos Policlorados/análisis , Japón , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Éteres , LípidosRESUMEN
Marine foods can be contaminated with organochlorines and the risk to human beings who consume these foods needs to be evaluated. We examined the teratogenic effects of contaminants extracted from whale bacon on rat embryos using a whole-embryo culture system. Embryonic day 11.5 embryos were cultured for 48 h with organohalogens extracted from whale bacon at low (polychlorinated biphenyls (PCBs): 0.32 ppm, dichlorodiphenyltrichloroethanes (DDTs): 0.16 ppm, chlordanes (CHLs): 0.02 ppm) and high (PCBs: 2.15 ppm, DDTs: 1.99 ppm, CHLs: 0.20 ppm) doses. The levels of organohalogen compounds in cultured embryos were determined. The organochlorine contaminants extracted from whale products were readily transferred to the cultured rat embryos. The number of heartbeats, yolk sac circulation score, and embryonic body circulation score of embryos did not change during the culture period in either exposure group. Cultured embryos treated with the low-dose contaminated medium for 48 h showed abnormalities of the mandible, and craniofacial or forelimb hematomas with an incidence of 50%. All embryos treated with the high-dose medium showed craniofacial abnormalities and cleft lip, and limb abnormalities and hematomas. These results indicate that the organohalogen contaminants in whale bacon may be teratogenic in a dose-dependent manner. Further studies are necessary to determine the dose-effect relationship.
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Hidrocarburos Clorados , Bifenilos Policlorados , Carne de Cerdo , Animales , Clordano , Hematoma , Humanos , Hidrocarburos Clorados/toxicidad , Bifenilos Policlorados/toxicidad , Ratas , BallenasRESUMEN
Concentrations of 16 metals in the scalp hair of male Crohn's disease (CD) patients (n = 28) were compared to those of male control subjects (n = 25). The majority of patients (n = 20) took an anti-inflammatory agent (mesalazine), and several patients underwent colectomy. A low concentration of serum ferritin was observed in approximately 50% of CD patients due to Fe-deficiency anemia. The concentrations of Fe, Cr, and Co in the hair of CD patients were significantly higher than those of control subjects, and particularly high concentrations were found in CD patients with low serum ferritin. Significant correlations were found among the concentrations of Fe, Cr, and Co in the hair of CD patients, but not in control subjects. In agreement with previous reports, a significant negative correlation was found between ferritin and transferrin concentrations in serum, although the available data in this study was limited (n = 8). Transferrin not only binds to Fe3+ but also to Cr3+ and Co3+, and the amount of transferrin is increased in Fe-deficiency anemia. Thus, the majority of the Fe3+, Cr3+, and Co3+ in the serum of CD patients is likely to bind to transferrin, which may be associated with the higher concentrations of those metals, as well as the significant correlations among those metals in the scalp hair of CD patients. In addition, colectomy may alter the intestinal absorption rate of some metals, while mesalazine may increase the concentrations of Mn and some metals in the scalp hair by chelate formation.
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Enfermedad de Crohn/diagnóstico , Cabello/química , Oligoelementos/análisis , Adolescente , Adulto , Humanos , Masculino , Metaloides/análisis , Persona de Mediana Edad , Cuero Cabelludo , Adulto JovenRESUMEN
We performed a detailed investigation of the uptake of sulfobromophthalein (BSP) from the apical membrane of Caco-2 cells, which is a substrate for organic anion transporting polypeptides (OATPs), and calculated the kinetic parameters of BSP uptake as follows: Km = 13.9 ± 1.3 µM, Vmax = 1.15 ± 0.07 nmol (mg protein)-1 (5 min)-1, and kd = 38.2 ± 0.53 µL (mg protein)-1 (5 min)-1. Coincubation with medium-chain (C7-C11) perfluoroalkyl carboxylic acids (PFCAs), such as perfluoroheptanoic acid (PFHpA, C7), perfluorooctanoic acid (PFOA, C8), perfluorononanoic acid (PFNA, C9), perfluorodecanoic acid (PFDA, C10) and perfluoroundecanoic acid (PFUnDA, C11), significantly decreased BSP uptake by 27-55%, while coincubation with short- (C3-C6) and long-chain (C12-C14) PFCAs decreased the uptake only slightly. Dixon plotting suggested that PFOA, PFNA and PFDA competitively inhibited the BSP uptake with inhibition constant (Ki) values of 62.2 ± 1.3 µM, 35.3 ± 0.1 µM and 43.2 ± 0.3 µM, respectively. PFCAs with medium-chains could be substrates for OATPs, probably OATP2B1, which is the most abundantly expressed OATP isoform in Caco-2 cells.
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The effects of Kanechlor-500 (KC500) on the levels of serum total thyroxine (T4 ) and hepatic T4 in wild-type C57BL/6 (WT) and its transthyretin (TTR)-deficient (TTR-null) mice were comparatively examined. Four days after a single intraperitoneal injection with KC500 (100 mg/kg body weight), serum total T4 levels were significantly decreased in both WT and TTR-null mice. The KC500 pretreatment also promoted serum [125 I]T4 clearance in both strains of mice administrated with [125 I]T4 , and the promotion of serum [125 I]T4 clearance in WT mice occurred without inhibition of the [125 I]T4 -TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady-state distribution volume of [125 I]T4 , hepatic accumulation level of [125 I]T4 , and concentration ratio of the liver to serum in both strains of mice. The present findings indicate that the KC500-mediated decrease in serum T4 level occurs in a TTR-unrelated manner and further suggest that KC500-promoted T4 accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T4 transportation from serum to liver.
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Hígado/efectos de los fármacos , Bifenilos Policlorados/toxicidad , Prealbúmina/metabolismo , Tiroxina/sangre , Animales , Glucuronosiltransferasa/metabolismo , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Bifenilos Policlorados/sangre , Prealbúmina/genética , Tirotropina/sangre , Tiroxina/metabolismo , Triyodotironina/sangreRESUMEN
Background/ Aim: A high polar xanthophyll of Fucoxanthin (Fx) is abundantly contained in edible brown algae, and it has chemopreventive effects in mouse cancer models, however, the underlying mechanisms of these effects are not well understood. Thus, we aimed to investigate the effects of Fx on the tumor microenvironment in cancer model mice. MATERIALS AND METHODS: We investigated the effect of Fx (30 mg/kg body weight) in a variety of cell types within the tumor microenvironment of α mouse preclinical colorectal cancer model and analyzed the mouse saliva in search of predictors for cancer chemopreventive effects. RESULTS: Fx administration significantly decreased the number of colorectal polyps and tended to decrease colonic lesions compared to untreated control mice. In addition, Fx administration showed significantly lower numbers of colorectal cancer stem cells-like CD44high/EpCAMhigh cells, cancer-associated fibroblasts-like αSMAhigh cells, tumor-associated macrophages-like and dendritic cells-like CD206high cells by 0.6-, 0.5- and 0.6-fold, respectively, compared to untreated control mice. Moreover, the treatment also showed significantly lower levels of salivary glycine by 0.5-fold. CONCLUSION: Our results suggest that salivary glycine may be a predictor representing the chemopreventive effect of Fx in mice.
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Neoplasias Colorrectales/tratamiento farmacológico , Glicina/genética , Pólipos/tratamiento farmacológico , Xantófilas/administración & dosificación , Animales , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Glicina/química , Humanos , Ratones , Pólipos/genética , Pólipos/patología , Saliva/química , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genéticaRESUMEN
Fucoxanthin and its major metabolite, fucoxanthinol, have potent anti-cancer properties in carcinogenic model mice and against cancer cells. Evidence has accumulated regarding the diagnostic potential of biological metabolites as invasive and non-invasive obtainable approaches. We recently demonstrated that glycine was an effective predictor of the suppression of sphere formation and epithelial mesenchymal transition by fucoxanthinol in human colorectal cancer stem-like spheroids (colonospheres) under normoxia and hypoxia. In the present study, we investigated the suppressive effect of fucoxanthin on tumorigenesis derived from colonospheres in xenograft mice, and the alteration on the metabolite profiles of mouse tumors by fucoxanthin was evaluated. Fucoxanthin administration at 2.5 mg/kg body weight (p.o.) for 4 weeks significantly inhibited the incidence of tumors by inoculation of colonospheres suspension in BALB/c nu/nu mice compared with control mice, but not tumor sizes. In addition, fucoxanthin down-regulated tumor Cyclin D1 expression by 0.7-fold of that observed in the tumors of the control mice. Moreover, the tumor glycine level in the xenograft mice was decreased by fucoxanthin administration to 0.5-fold. These results imply the possibility of tumor metabolites as a prediction marker of tumorigenicity derived from colorectal cancer stem cells in mice.
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We investigated the profiles and levels of perfluoroalkyl carboxylic acid (PFCA) contamination in Pacific cod (Gadus macrocephalus) from the North Pacific Ocean. The mean concentrations of PFCAs containing 8 to 14 carbon atoms (C8-C14) in edible Pacific cod muscle ranged from 216 to 670â¯pgâ¯g-1 wet weight in the Northeast Pacific Ocean (Seattle, Vancouver, Alaska, and Russia), from 819 to 1710â¯pgâ¯g-1 wet weight in Japanese coastal waters (Hokkaido, Aomori, Iwate, Miyagi, Tottori, and Shimane), and from 288 to 892â¯pgâ¯g-1 wet weight in Korean waters (Sokcho, Busan, and Yeosu). These results indicate there are geographical differences in the distribution of PFCAs. The long-chain PFCAs (C9-C14) contributed 96% of the total PFCA concentration across Japan, whereas they contributed only 33% of the total PFCA concentration in the USA and Canada. Long-chain PFCA concentrations in cod samples collected in Japanese and Korean waters were about three to four times those in samples from the USA, Canada, and Russia. Because seafood is considered an important dietary source of PFCAs, high concentrations of long-chain PFCAs in Pacific cod from Japanese and Korean waters may affect human dietary exposure and blood concentrations of long-chain PFCAs.
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Monitoreo del Ambiente , Fluorocarburos/metabolismo , Gadiformes/metabolismo , Contaminantes Químicos del Agua/metabolismo , Alaska , Animales , Canadá , Ácidos Carboxílicos/análisis , Fluorocarburos/análisis , Japón , Músculos/química , Océano Pacífico , Federación de RusiaRESUMEN
RATIONALE: Elental® is an elemental diet widely used as a nutritional supplement for Crohn's disease (CD) patients in Japan. Elental® contains amino acids as nitrogen sources and does not contain selenium (Se), and the δ13 C and δ15 N values of Elental® are markedly higher and lower, respectively, than those of a normal diet. METHODS: We compared the δ13 C and δ15 N values and Se concentration in the scalp hair of CD patients with those of control subjects who ate a regular diet, and estimated the amount of Elental® ingested as a supplement. The δ13 C and δ15 N values and the Se concentrations were quantified using isotope ratio mass spectrometry (IRMS) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. RESULTS: An increase in Elental® ingestion increased the δ13 C value in the hair of CD patients (p <0.05), while it reduced the δ15 N value (p <0.05) and tended to reduce the Se concentration in female patients. CONCLUSIONS: The amount of Elental® ingested could be estimated by the δ13 C and δ15 N values in the hair of CD patients. Furthermore, the Se deficiency in female patients may be predicted from the δ13 C and δ15 N values.
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Isótopos de Carbono/análisis , Enfermedad de Crohn/dietoterapia , Alimentos Formulados , Cabello/química , Isótopos de Nitrógeno/análisis , Adulto , Estudios de Casos y Controles , Suplementos Dietéticos , Ingestión de Energía , Femenino , Humanos , Lípidos/farmacocinética , Masculino , Espectrometría de Masas/métodos , Evaluación Nutricional , Cuero Cabelludo , Selenio/análisisRESUMEN
Fucoxanthin (Fx) and its biotransformed fucoxanthinol (FxOH) present strong anti-cancer effects in vitro and in vivo, however, the underlying mechanisms are not well known. We recently demonstrated that FxOH could induce anoikis-like cells in human colorectal cancer (CRC) cells. Thus, we developed molecular hallmarks for anoikis in vitro, and to confirm induction of such molecular hallmarks in an azoxymethane/ dextran sodium sulfate carcinogenic model by Fx ingestion. During the process of anoikis by FxOH (2.5 µmol/l) in DLD-1 cells, the cells show the characteristics of integrin ß1low/-, p-FAK(Tyr397)low/- or p-Paxillin(Tyr31)low/- cells with cleaved caspase-3high, which may be useful as molecular hallmarks. Fx administration (30 mg/kg body weight) significantly suppressed the number and size of polyps compared with untreated control mice. In addition, the incidence and multiplicity of colonic lesions tended to reduce. Moreover, cells showing integrin ß1low/-, p-FAK(Tyr397)low/- and p-Paxillin(Tyr31)low/- with cleaved caspase-3high in colonic crypts were significantly increased 2.2-, 4.8- and 5.2-fold by Fx administration compared with untreated control mice, respectively. Our results suggest that Fx showed a chemopreventive effect in the carcinogenic models through anoikis-like cells induction.
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Anoicis/efectos de los fármacos , Neoplasias Colorrectales/prevención & control , Xantófilas/farmacología , Animales , Anticarcinógenos/farmacología , Azoximetano/toxicidad , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Sulfato de Dextran/toxicidad , Humanos , Integrina beta1/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Ratones Endogámicos ICR , Paxillin/metabolismo , Proteínas/metabolismoRESUMEN
Levels and profiles of naturally produced halogenated bipyrroles (Br4Cl2-DBP and Cl7-MBP), methoxylated tetrabromodiphenyl ethers (6-MeO-BDE47), anthropogenic perfluoroalkyl substances (PFASs) and legacy persistent organic pollutants (POPs) were investigated in the livers of 14 cetaceans from the Sea of Japan and the North Pacific Ocean. The concentrations of Br4Cl2-DBP (4 to 4900â¯ng/g-wet), Cl7-MBP (16 to 3960â¯ng/g-wet) and 6-MeO-BDE47 (7 to 190â¯ng/g-wet) were higher in the order of killer whalesâ¯>â¯toothed whalesâ¯>â¯baleen whales. Profiles of PFASs were dominated by perfluoroundecanoic and perfluorotridecanoic acids (10 to 540â¯ng/g-wet), sum of which accounted for 70% of total measured PFASs. Regional difference was observed for Cl7-MBP and PFASs, which were higher in the Sea of Japan, whereas Br4Cl2-DBP was in the North Pacific Ocean. Specific accumulation pattern of these natural contaminants in cetaceans around northern Japan could help compare the exposure profile of PFASs and POPs among other geographic regions.
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Cetáceos , Hidrocarburos Halogenados/análisis , Hígado/química , Contaminantes Químicos del Agua/análisis , Animales , Monitoreo del Ambiente , Femenino , Hidrocarburos Halogenados/química , Japón , Masculino , Océano Pacífico , Pirroles/análisis , Pirroles/química , OrcaRESUMEN
Essential elements (Ca, Mg, Zn, Cu, Fe, Cr, Mn and V) and non-essential elements (As, Cd, Hg and Pb) were measured in scalp hair samples of 45 diabetic subjects and 59 control subjects in Japan using inductively coupled plasma mass spectrometry. All diabetic subjects took insulin and/or antidiabetic agents, with glycated hemoglobin (HbA1c) ranging between 6.2 and 14.4%. The levels of Zn, Cu and Cr in the diabetic subjects (HbA1c>7) were significantly lower than those in the control subjects (p<0.05), and these concentrations decreased significantly with increases in HbA1c (p<0.01). The levels of Fe and Mg in the diabetic subjects were insignificantly lower, and the concentration of Fe decreased significantly with increases in HbA1c (p<0.05) and the concentration of Mn tended to decrease (p<0.10). In contrast, the concentration of As tended to increase with increases in HbA1c (p<0.10). The concentrations of other elements, such as Ca, Mn, V, Pb, Cd and Hg, in the diabetic subjects were similar to those of control subjects, and did not correlate with HbA1c. The average of estimated glomerular filtration rate (eGFR) in the diabetic subjects was 77.7±29.7 mL/min/1.73 m2 with large variation (12.7-148 mL/min/1.73 m2), and previous study reported the increase of urinary excretion of Zn, Cr, Mn and Mg in diabetic subjects. The decreases of Zn, Cu, Cr, Fe and Mg concentrations in hair may reflect increased urinary excretion of these elements due to diabetic nephropathy.
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Diabetes Mellitus/metabolismo , Hemoglobina Glucada/análisis , Cabello/química , Oligoelementos/análisis , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Diabetes Mellitus/sangre , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Cuero CabelludoRESUMEN
Fucoxanthinol (FxOH) is a strong anticancer metabolite of fucoxanthin that accumulates in abundance in edible brown algae and promises human health benefits. FxOH has been shown to suppress tumorigenicity and sphere formation in human colorectal cancer stem cell (CCSC)-like spheroids (colonospheres, Csps). In the present study, we aimed to clarify the inhibitory activity of FxOH on epithelial-mesenchymal transition (EMT), which is essential for cancer recurrence and distant metastasis, and to identify intracellular low-molecular-weight metabolites that may be useful for evaluating the cellular effects of FxOH on CCSCs. FxOH significantly suppressed sphere-forming activity, migration and invasion in a dose-dependent manner. In addition, treatment with 50 µmol/l FxOH suppressed N-cadherin and vimentin expression and the activation of integrin signaling linked to EMT suppression by western blot analysis. MAPK signaling and STAT signaling related to cell growth and apoptosis in Csps derived from human CRC HT-29 and HCT116 cells were also altered. According to our metabolite profiling by GC-MS analysis, reduced glycine and succinic acid levels were correlated with EMT suppression and apoptosis induction in Csps. Our data indicate that simple amino acids such as glycine and succinic acid may be good prognostic indicators of physiological changes to CCSCs induced by FxOH treatment.
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Neoplasias Colorrectales/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , beta Caroteno/análogos & derivados , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glicina/metabolismo , Células HCT116 , Células HT29 , Humanos , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Células Madre Neoplásicas/patología , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Ácido Succínico/metabolismo , beta Caroteno/farmacologíaRESUMEN
BACKGROUND/AIM: Fucoxanthinol (FxOH), a metabolite of fucoxanthin, is known to inhibit tumorigenicity of human colorectal cancer stem cells (CCSCs) and their sphere formation. Hypoxic conditions and hypoxia-inducible factors (HIFs) are essential to maintain the stemness of CCSCs. We investigated effects of FxOH on sphere formation, intercellular energy metabolites in colonospheres formed from human colorectal HT-29 cells under hypoxic conditions. RESULTS: FxOH at 50 µM suppressed HIF1α expression and activation of integrin, mitogen-activated protein kinase (MAPK), Wingless/integrated (WNT) and signal transducer and activator of transcription (STAT) signals. Moreover, expression of epithelial-mesenchymal transition- and apoptosis-related proteins in the colonospheres was lowered by FxOH. The level of glycine was reduced in hypoxic colonospheres under FxOH treatment. CONCLUSION: FxOH attenuated the sphere formation of hypoxic colonospheres, in part, by suppressing HIF1α expression. Glycine could be a potential predictor for the activity of agents that inhibit sphere formation by hypoxic colonospheres.
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Biomarcadores de Tumor , Glicina/fisiología , Hipoxia/patología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/patología , beta Caroteno/análogos & derivados , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Proliferación Celular/efectos de los fármacos , Monitoreo de Drogas/métodos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Glicina/análisis , Glicina/metabolismo , Células HT29 , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , beta Caroteno/farmacologíaRESUMEN
Hokkaido, the northernmost of the main islands of Japan, is surrounded by the North Pacific Ocean, the Japan Sea and the Okhotsk Sea, and three independent stocks of Pacific cod are thought to inhabit those three areas. The Fukushima Dai-ichi Nuclear Power Plant (FDNPP), which is located in the north of Honshu, the main island of Japan, was disputed in 2011. Most of the radiocesium from the FDNPP was released into the western North Pacific Ocean, and the biota in those areas were considerably contaminated soon after the FDNPP accident. We analyzed radiocesium in Pacific cod caught around Hokkaido between 2011 and 2015. The radiocesium was predominantly detected in the cod caught in the North Pacific Ocean, and not in those caught the Japan Sea and the Okhotsk Sea. These results suggest that the cod caught in the Pacific Ocean around Hokkaido moved through the contaminated area off the FDNPP.
Asunto(s)
Radioisótopos de Cesio/análisis , Accidente Nuclear de Fukushima , Gadiformes , Plantas de Energía Nuclear , Monitoreo de Radiación/métodos , Contaminantes Radiactivos del Agua/análisis , Animales , Isótopos de Carbono/análisis , Japón , Músculos/química , Isótopos de Nitrógeno/análisis , Océano PacíficoRESUMEN
Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches.