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.
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 β1low/−, 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 β1low/−, 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.
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 Fe
3+
but also to Cr
3+
and Co
3+
, and the amount of transferrin is increased in Fe-deficiency anemia. Thus, the majority of the Fe
3+
, Cr
3+
, and Co
3+
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.
We analyzed Hg, Cd, Zn, Cu and Fe concentrations in liver samples as well as the Hg concentration and stable isotope ratios of carbon and nitrogen (δ13C and δ15N) in muscle samples from silvertip ...sharks (Carcharhinus albimarginatus) in Japan. Muscular and hepatic Hg concentrations increased with increased body length. However, these increases were more prominent in the liver than in the muscle samples, and appeared to occur after maturation. Hepatic Zn and Cu concentrations decreased during the growth stage, and then increased concomitantly thereafter with increases in Cd burden. Hepatic Fe concentration from males increased proportionally with increases in body length, whereas no increase was observed in samples from females, probably due to the mother-to-embryo transfer of Fe. The δ13C values tended to decrease with increases in body length, whereas no decrease in the δ15N values was observed.
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 β-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 β-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 β-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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•Dicofol, endosulfans, mirex, and toxaphenes in Japanese breast milk were measured.•Regional differences in the concentrations of several pollutants were found.•Lipid-weight endosulfan concentrations negatively correlated with the lipid contents.•Toxaphene concentrations positively correlated with the lipid contents.•PCA indicated that endosulfans and toxaphenes have different kinetics from other POPs.
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 670 pg g−1 wet weight in the Northeast Pacific Ocean (Seattle, Vancouver, Alaska, and Russia), from 819 to 1710 pg g−1 wet weight in Japanese coastal waters (Hokkaido, Aomori, Iwate, Miyagi, Tottori, and Shimane), and from 288 to 892 pg 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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•Perfluoroalkyl carboxylic acids were detected in edible muscle from North Pacific cod.•PFCA profiles varied around the North Pacific regions.•C11, C12, and C13 PFCA levels in East Asia were higher than those at the other sites.•These high concentrations in fish may result in high dietary exposure for humans.
Long-chain PFCA concentrations in cod are high in Japan, and may be related to human serum concentrations.
•Uptake of perfluorooctanoic acid (PFOA) was investigated using Caco-2 cells.•Uptake of PFOA was fast, and pH and temperature dependent, but Na+ independent.•BSP (a typical substrate of OATPs) ...competitively inhibited the uptake of PFOA.•Uptake of PFOA could be, at least in part, mediated by OATPs along with BSP.
The mechanism underlying the intestinal absorption of perfluorooctanoic acid (PFOA) was investigated using Caco-2 cells. The uptake of PFOA from the apical membrane of Caco-2 cells was fast, and pH, temperature, and concentration dependent, but Na+ independent. Coincubation with sulfobromophthalein (BSP), glibenclamide, estron-3-sulfate, cyclosporine A or rifamycin SV, which are typical substrates or inhibitors of organic anion transporting polypeptides (OATPs), significantly decreased the uptake of PFOA. However, coincubation with probenecid or p-aminohippuric acid, typical substrates of organic anion transporters, did not decrease the uptake of PFOA. Furthermore, coincubation with l-lactic acid or benzoic acid, substrates of monocarboxylic acid transporters, did not decrease PFOA uptake. The relationship between the initial uptake of PFOA and its concentration was saturable, suggesting the involvement of a carrier-mediated process. The calculated Km and uptake clearance (Vmax/Km) values for PFOA were 8.3μM and 55.0μL/mg protein/min, respectively. This clearance value was about 3-fold greater than that of the non-saturable uptake clearance (Kd: 18.1μL/mg protein/min). Lineweaver–Burk plots revealed that BSP competitively inhibits the uptake of PFOA, with a Ki value of 23.1μM. These results suggest that the uptake of PFOA from the apical membranes of Caco-2 cells could be, at least in part, mediated by OATPs along with BSP.
The aim of this study was to compare the δ15N, δ13C, Hg and organochlorines (PCBs, p,p′-DDE and trans-nonachlor) in the yellowfin tuna taken from several regions of the Pacific and Indian Oceans. The ...highest values of δ15N and δ13C were observed in the tuna taken from Sri Lanka and Maldives (Indian Ocean), while the lowest values were observed in the tuna taken from Hawaii. In contrast, the highest Hg concentration was observed in the tuna taken from Hawaii, while the lowest concentration was observed in the tuna taken from Sri Lanka and Maldives. These orders of δ15N, δ13C and Hg may reflect the geographical characteristics of those among nine regions. On the other hand, the highest concentration of each organochlorine was found in the tuna taken from New Zealand, while the lowest was found in the tuna sample from Hawaii, probably reflecting the anthropogenic contamination among eight regions. The inter-regional variations in organochlorines were markedly larger than those in Hg concentration. The Hg uniformly distributed in the area under the normal curve of Hg concentration against δ13C or δ15N value, while the organochlorines did not. This difference may be ascribed to the fact that Hg is of natural and anthropogenic origins, while the organochlorines are of anthropogenic origin. A principal compartment analysis of δ13C, δ15N, Hg and organochlorines apparently clarified the tuna taken from eight regions into 5 groups of Sri Lanka and Maldives, New Zealand, Australia, Hawaii and Japan.
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 4900 ng/g-wet), Cl7-MBP (16 to 3960 ng/g-wet) and 6-MeO-BDE47 (7 to 190 ng/g-wet) were higher in the order of killer whales > toothed whales > baleen whales. Profiles of PFASs were dominated by perfluoroundecanoic and perfluorotridecanoic acids (10 to 540 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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•Halogenated bipyrroles and methoxy-PBDEs accumulated in the livers of cetaceans.•Long-chained perfluoroalkyl carboxylates (PFCAs) largely exceeded the sulfonates.•No correlation was detected between natural products and long-chain PFCAs.•Bipyrrole and long-chain PFCA profiles differed in cetaceans from two regions.
Repair from traumatic bone fracture is a complex process that includes mechanisms of bone development and bone homeostasis. Thus, elucidation of the cellular/molecular basis of bone formation in ...skeletal development would provide valuable information on fracture repair and would lead to successful skeletal regeneration after limb amputation, which never occurs in mammals. Elucidation of the basis of epimorphic limb regeneration in amphibians would also provide insights into skeletal regeneration in mammals, since the epimorphic regeneration enables an amputated limb to re‐develop the three‐dimensional structure of bones. In the processes of bone development, repair and regeneration, growth of the bone is achieved through several events including not only cell proliferation but also aggregation of mesenchymal cells, enlargement of cells, deposition and accumulation of extracellular matrix, and bone remodeling.
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