Iron is an essential trace element for normal functions of the body. Restriction of iron availability directly limits erythropoiesis. The objective of this experiment was to compare the bioavailability of iron nanoparticles (Fe-NPs) with iron-microparticles (Fe-MPs) in anemic mice. There were four experimental groups, including the normal control group, iron-deficiency anemia (IDA) group, Fe-NPs group, and Fe-MPs group. Animals in the normal group fed on an adequate iron-containing diet (45 ppm Fe). Meanwhile, animals in the other three groups fed on a low Fe diet (4.5 ppm Fe) for seven weeks. Double deionized water was supplied as drinking water ad libitum. After feeding for three weeks with the low Fe diet, animals in the Fe-NPs and Fe-MPs groups received oral administration of Fe-NPs or Fe-MPs at a daily dose of 40 mg/kg for four weeks. The IDA group showed markedly decreased red blood cell (RBC) count, hematocrit (Hct), and hemoglobin (Hb) values compared with the normal group throughout the experimental periods. Treatments with Fe-NPs or Fe-MPs for four weeks resulted in restoration of the decreased RBC count and hematological values similar to normal values. The Fe-NPs group showed faster restoration in values than Fe-MPs with passage of time. The iron contents of the upper small intestine in the Fe-NPs and Fe-MPs groups were higher than in the normal group at weeks 2 and 4. Treatment with Fe-NPs and Fe-MPs resulted in a significant increase in hepatic iron contents and lipid peroxidation, compared with the IDA group with passage of time. The iron contents in liver and ferritin deposits in spleen were identified in the Fe-NPs and Fe-MPs groups, similar to the normal group. These results indicate that oral administration of both Fe-NPs and Fe-MPs can result in recovery from anemia and Fe-NPs is more absorbable and available in the body than Fe-MPs.

The nasal cavity encounters various irritants during inha¬lation such as dust and pathogens. To detect and remove these irritants, it has been postulated that the nasal mucosa epithelium has a specialized sensing system. The oral cavity, on the other hand, is known to have bitter taste receptors (T2Rs) that can detect harmful substances to prevent ingestion. Recently, solitary chemosensory cells expressing T2R subtypes have been found in the respiratory epithelium of rodents. In addition, T2Rs have been identified in the human airway epithelia. However, it is not clear which T2Rs are expressed in the human nasal mucosa epithelium and whether they mediate the removal of foreign materials through increased cilia movement. In our current study, we show that human T2R receptors indeed function also in the nasal mucosa epithelium. Our RT-PCR data indicate that the T2R subtypes (T2R3, T2R4, T2R5, T2R10, T2R13, T2R14, T2R39, T2R43, T2R44, T2R 45, T2R46, T2R47, T2R48, T2R49, and T2R50) are expressed in human nasal mucosa. Furthermore, we have found that T2R receptor activators such as bitter chemicals augments the ciliary beating frequency. Our results thus demonstrate that T2Rs are likely to function in the cleanup of inhaled dust and pathogens by increasing ciliary movement. This would suggest that T2Rs are feasible molecular targets for the development of novel treatment strategies for nasal infection and inflammation.

True hermaphrodites are animals of equivocal sex in which both male and female gonads develop simultaneously. The frequency of true hermaphroditism is higher in pigs than in other domestic animals. Two Korean pigs were diagnosed with true hermaphroditism showing ovotestes, epididymes, penes, and uteri. Histomorphologically, the testicular tissues consisted of Sertoli cells that were devoid of spermatogenic germ cells and showed proliferation of interstitial cells. However, the uteri were of normal architecture and had well-developed uterine endometrial glands. The samples were 38, XX female karyotype without the sex-determining region Y (SRY) gene. The findings of this study could contribute to the understanding of true hermaphroditism in the Korean pig industry. * This work was supported by a grant (Code# PJ008148) from BioGreen21 Program, Rural Development Administration, Republic of Korea.

Both iron-deficient and zinc-sufficient diets have been known to be associated with a decreased risk of colon cancer. We investigated that effect of dietary zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM) followed by dextran sodium sulfate in iron-deficient mice. Five-week old ICR mice were acclimated for 1 week and fed on iron-deficient diet (4.50 ppm iron) with three different zinc levels (0.01, 0.1, and 1.0 ppm) for 12 weeks. The total number of aberrant crypt (AC) and ACF was measured in the colonic mucosa after methylene blue staining. The total ACF numbers of low Zn (LZn), medium Zn (MZn) and high Zn (HZn) diet groups were 10.00 ± 2.67, 8.78 ± 3.12, and 7.96 ± 2.44, respectively and there were no significant differences among the groups. However, the total AC numbers of HZn (27.07 ± 3.88) and MZn (26.39 ± 5.59) diet groups were significantly low compared to LZn (22.57 ± 5.09) diet group (p<0.01). Cytosolic SOD activity was the highest in LZn diet group. But thiobarbituric acid-reactive substances level in liver was also the highest in LZn diet group compared to other groups. There is no difference in cell proliferation in mucous membrane among the groups, while apoptotic positive cells were increased in the HZn diet group. The high zinc diet exhibited decreased β-catenin-stained areas on the mucous membrane of colon compared to the LZn or MZn diet group. These findings indicate that dietary zinc might exert a modulating effect on development of ACF/AC in the mice with iron-deficient status.

Iron nanoparticles (Fe-NPs) have recently been used for cancer diagnosis and therapy for imaging contrast and drug delivery. However, no study on nutritional bioavailability of Fe-NPs in the body has been reported. Ascorbic acid (AA) is known to aid in absorption of iron in the stomach by reducing Fe (III) to Fe (II). In this study, we investigated the bioavailability of Fe-NPs with AA in iron-deficiency-anemic mice in comparison with non-nano iron particles. Iron-deficient anemia was induced by feeding an iron-deficient diet (4.5 mg Fe/kg) and ocular bleeding from retro-orbital venous plexus for four weeks. Normal control mice were given a normal diet (45 mg Fe/ kg). After induction of anemia in mice, anemic mice received daily oral administration of Fe (40 mg/kg B.W.) + AA (5 g/kg B.W) and Fe-NPs (40 mg/kg B.W) + AA (5 g/kg B.W). After sacrifice, liver and spleen tissues were observed by haematoxylin & eosin stain. Amount of trace iron in liver and upper small intestine was investigated using an inductively coupled plasma-atomic emission spectrometer. Red blood cells (RBC), hematocrit (Hct), hemoglobin (Hb), and total iron binding capacity were also measured. The concentrations of iron in the Fe-NPs + AA group were significantly higher in liver and in upper small intestine than that in the Fe + AA group. The values of RBC, Hct, and Hb in the Fe-NPs + AA group were more rapidly increased to normal values compared with the Fe + AA group with increasing time. These results suggest that Fe-NPs in the presence of AA may be more bioavailable than non-nano Fe in Fe-deficient anemic mice.

The objective of this study was to determine the effect of macrophages on growth of human colon cancer cells. The results showed that co-culture of colon cancer cells with macrophages inhibited the growth of colon cancer cells (HCT116 and SW620) depending on the number of macrophages, RAW 264.7 cells, and activated THP-1 cells accompanied by down regulation of pSTAT3 in cancer cells. We also found that expression and release of cancer cell growth inhibitory cytokines, IL-1 receptor antagonist (IL-1ra) and IL-10, was increased in macrophages. Blocking of the STAT3 pathway with specific inhibitor and siRNA of STAT3 abolished the growth of colon cancer cells and expression of IL-1ra and IL-10. In addition, neutralization of IL-1ra and IL-10 with antibodies resulted in reversal of macrophage-induced inhibition of cancer cell growth. These data showed that IL-1ra and IL-10 released from macrophages inhibit growth of colon cancer cells through inhibition of the STAT3 pathway.

Plasma glutathione peroxidase (pGPx) is an extracellular antioxidative selenoenzyme which has been detected in various adult tissues, but little is known about the expression and distribution of pGPx during embryogenesis. To investigate the expression patterns of pGPx during embryogenesis, we performed quantitative real-time PCR, in situ hybridization, Western blot, and immunohistochemistry analyses in whole embryos or each developing organ of mice on embryonic days (E)7.5–18.5. In whole embryos of E7.5–8.5, pGPx mRNA was more typically expressed in extra-embryonic tissues including ectoplacental cone, trophectoderm, and decidual cells than in embryos. However, after E9.5, pGPx mRNA and protein levels were increased in the embryos with differentiation and growth, but trended to gradually decrease in the extra-embryonic tissues until E18.5. In sectioned embryonic tissues on E13.5–18.5, pGPx mRNA and protein were mainly expressed in the developing nervous tissues, the sensory organs, and the epithelia of lung, skin, and intestine, the heart and artery, and the kidney. In particular, pGPx immunoreactivity was very strong in the developing liver. These results indicate that pGPx is spatio-temporally expressed in various embryonic organs as well as extra-embryonic tissues, suggesting that pGPx may function to protect the embryos against endogenous and exogenous reactive oxygen species during organogenesis.

Nicotine, a major teratogen of cigarettes smoke induces embryonic abnormalities during the early stages of organogenesis. In this study, the protective effect of β-carotene against nicotine–induced embryos was evaluated by morphologic scoring, nile blue staining, lipid peroxidation, SOD activity assay and real-time PCR. The embryos exposed to nicotine (1 μM) revealed remarkable morphological anomalies compared to normal control group (p<0.05), but when β-carotene (1×10‒4 μM or 5×10‒4 μM) was added concurrently to the embryos exposed to nicotine, morphological parameters were significantly improved (p<0.05). Nicotine induced oxidative stress by increased lipid peroxidation, expression of proinflammatory cytokines (TNF-α and IL-1β), caspases-3 and decreased SOD activity. However, administration of β-carotene (1×10‒4 μM or 5×10‒4 μM) restored the SOD level and decreased oxidative damage in the embryos. These results indicate that β-carotene effectively counteracts the deleterious effects of nicotine on embryos and attenuates oxidative damage possibly through its antioxidant effects.

Nicotine, a major toxic component in tobacco smoke, leads to severe embryonic damages on organogenesis. We investigated if resveratrol can inhibit the nicotine–induced teratogenesis in the cultured mouse embryos (embryonic day 8.5) for 48 hours using a whole embryo culture system. The embryos exposed to nicotine (1 μM) revealed severe morphological anomalies, the increased levels of caspase-3 mRNA and lipid peroxidation, and further the lowered levels of mitochondrial manganese superoxide dismutase (SOD), cytosolic glutathione peroxidase (GPx), phospholipid hydroperoxide GPx, hypoxia-inducible factor 1α, and sirtuin mRNAs and SOD activity significantly compared to normal control group (p<0.05). However, whenre sveratrol(1×10‒5 μMor1 ×10‒4 μM) was added concurrently to the embryos exposed to nicotine, these all parameters were significantly improved (p<0.05).These findings indicate that resveratrol has a protective effect against nicotine-induced teratogenesis in mouse embryos throughout antioxidative and anti-apoptotic activities.

The current study was conducted in order to investigate promotional effects of herbal extracts on hair growth in an animal model of mice. There were four experimental groups, including distilled water (DW) as a negative control (NC), 3% minoxidil (MXD) as a positive control (PC), 50% ethanol (EtOH) as a vehicle control (VC), and herbal extract (HE) as the experimental treatment (E). The HE was extracted with ethanol from plants, including Gardenia, Mentha arvensis, Rosemary, and Lavender. Six-week-old C57BL/6 male mice were shaved with an electric clipper and the test materials were topically treated with 0.2 ml per mouse daily for three weeks. Photographic evaluation of hair re-growth was performed weekly during a period of three weeks. The number of mast cells was counted on the dorsal skin section of mice. The enzymes, alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GT), were determined using a biochemical autoanalyzer. No clinical signs were observed in any of the experimental groups. As a result of photometric analysis, topical application of HE to dorsal skin for two weeks resulted in significantly faster acceleration of hair regrowth, compared with that of the NC or VC group (P<0.05). The PC and E groups showed a significant decrease in mast cell population, compared to the NC group. Activities of ALP and γ-GT were significantly increased in the PC and E groups, compared to the NC or VC group (P<0.05). Taken together, these results suggest that the herbal extract may have hair-growth promoting activity equal to that of MXD.

Zinc oxide nanoparticles (nZnO) are used in a various range, including ceramic manufacture, photocatalysis, UV filters, and the food industry. However, little is known about the effects of micro- and nano-particles during mouse embryo organogenesis. To determine whether ZnO affects size-dependent anomalies during embryonic organogenesis, mouse embryos were cultured for two days with 300 ug/ml micro ZnO (mZnO;80±25 μm) and nZnO (< 100 nm) and the developmental changes were then investigated. Quantity of Zn by inductively coupled plasma mass spectrometry analysis, and expression patterns of various antioxidant enzymes in the embryos were investigated. Embryos exposed to mZnO or nZnO exhibited severe retardation of growth and development. In embryos exposed to mZnO and nZnO, yolk sac diameter, crown-rump length, and head length were significantly diminished. The morphological parameters, including yolk sac circulation, allantois, flexion, heart, hindbrain, midbrain, forebrain, otic system, optic system, branchial bars, maxillary process, mandibular process, olfactory system, caudal neural tube, forelimb, hindlimb, and somites in mZnO and nZnO-treated groups were significantly decreased. Zn absorption of the nZnO-treated group was significantly higher than that of the mZnO-treated group. Significantly decreased levels of CuZn-SOD, Mn-SOD, cGPx, and PHGPx mRNA were observed in the ZnO-treated group. In addition, antioxidant enzyme mRNA expressions of the nZnO group were significantly diminished, less than those of the mZnO treated group. These findings indicate that 300 ug/ml ZnO showed abnormality and nZnO may have a more severe effect than mZnO in developing embryos.