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The mixture of 5-chloro-2-methylisothiazol-3(2H)-one (CMIT) and 2-methylisothiazol-3(2H)-one (MIT), CMIT/MIT, is a preservative in cosmetics. CMIT/MIT is a highly effective preservative; however, it is also a commonly known skin sensitizer. Therefore, in the present study, a risk assessment for safety management of CMIT/MIT was conducted on products containing 0.0015% of CMIT/MIT, which is the maximum MIT level allowed in current products. The no observed adverse effect level (NOAEL) for CMIT/MIT was 2.8 mg/kg bw/day obtained from a two-generation reproductive toxicity test, and the skin sensitization toxicity standard value for CMIT/MIT, or the no expected sensitization induction level (NESIL), was 1.25 μg/cm2/day in humans. According to a calculation of body exposure to cosmetics use, the systemic exposure dosage (SED) was calculated as 0.00423 mg/kg bw/day when leave-on and rinse-off products were considered. Additionally, the consumer exposure level (CEL) amounted to 0.77512 μg/cm2/day for all representative cosmetics and 0.00584 μg/cm2/day for rinse-off products only. As a result, the non-cancer margin of safety (MOS) was calculated as 633, and CMIT/MIT was determined to be safe when all representative cosmetics were evaluated. In addition, the skin sensitization acceptable exposure level (AEL)/CEL was calculated as 0.00538 for all representative cosmetics and 2.14225 for rinse-off products; thus, CMIT/MIT was considered a skin sensitizer when all representative cosmetics were evaluated. Current regulations indicate that CMIT/MIT can only be used at concentrations 0.0015% or less and is prohibited from use in other cosmetics products. According to the results of this risk assessment, the CMIT/MIT regulatory values currently used in cosmetics are evaluated as appropriate.

Triclosan (TCS) is an antimicrobial compound used in consumer products. The purpose of current study was to examine toxicology and risk assessment of TCS based on available data. Acute toxicities of oral, transdermal and inhalation routes were low, and phototoxicity and neurotoxicity were not observed. Topical treatment of TCS to animal caused mild irritation. TCS did not induce reproductive and developmental toxicity in rodents. In addition, genotoxicity was not considered based on in vitro and in vivo tests of TCS. It is not classified as a carcinogen in international authorities such as International Agency for Research on Cancer (IARC). No-observed-adverse-effect level (NOAEL) was determined 12 mg/kg bw/day for TCS, based on haematoxicity and reduction of absolute and relative spleen weights in a 104-week oral toxicity study in rats. Percutaneous absorption rate was set as 14%, which was human skin absorption study reported by National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (2009). The systemic exposure dosage (SED) of TCS has been derived by two scenarios depending on the cosmetics usage of Koreans. The first scenario is the combined use of representative cosmetics and oral care products. The second scenario is the combined use of rinse-off products of cleansing, deodorants, coloring products, and oral care products. SEDs have been calculated as 0.14337 mg/kg bw/day for the first scenario and 0.04733 mg/kg bw/day for the second scenario. As a result, margin of safety (MOS) for the first and second scenarios was estimated to 84 and 253.5, respectively. Based on these results, exposure of TCS contained in rinse-off products, deodorants, and coloring products would not pose a significant health risk when it is used up to 0.3%.

As an alternative to animal tests for skin sensitization potency and risk assessment, cell viability and biomarkers related to skin sensitization were analyzed in THP-1 human monocytic leukemia cells. Cell viabilities of 90% (CV90) and 75% (CV75) were determined for 24 selected test chemicals. Further biomarkers related to skin sensitization were also determined under equivalent comparative conditions. In cell viability analyses, potent skin sensitizers exhibited high cytotoxicity, but non-sensitizers did not display this tendency. In biomarker analyses, interleukin-I beta (IL-1β), inducible nitric oxide synthase (iNOS), IL-1β+iNOS, and THP-1 IL-1β+Raw 264.7 IL-1β were found to be suitable for prediction of skin sensitization potency following classification as either skin sensitizers or non-sensitizers (accuracies of 91.7%, 87.5%, 83.3%, and 82.6%, respectively). A significant positive correlation was found between biomarkers and skin sensitization potency, with a correlation coefficient (R) of 0.7 or more (correlation coefficients of 0.77, 0.72, 0.7, and 0.84, respectively). Finally, the skin sensitization potency effective threefold concentration (EC) 3% was predicted using a biomarker equation, with resulting prediction rates (match rate with actual data) of 58.3%, 54.2%, 62.5%, and 60.9%, respectively. The prediction accuracy for the EC3 value obtained from animal data was calculated as 83.3%, 79.2%, 79.2%, and 73.9%, respectively. Thus, these biomarkers, IL-1β and iNOS, may be alternatively used to predict skin sensitization potency and risk assessment.

A risk assessment was performed for three types of phthalates, benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl)phthalate (DEHP) unintentionally contaminated in cosmetics. A total of 100 products of 8 types of cosmetics were analyzed employing gas chromatography-mass spectrometry (GC-MS). By applying the maximum detected values of phthalates based on the worst exposure cases, their systemic exposure dosage (SED) was calculated. Accordingly, DEHP was identified as the main unintentional phthalates contaminants (0.10–600.00 ppm) in the cosmetics, with an SED of 3.37 × 10−9–3.75 × 10−4 mg/kg/day. In the non-cancer risk assessment, a margin of safety (MOS ≥ 100, safe) of 1.28 × 104–1.42 × 109 was estimated. In the cancer risk assessment, the lifetime cancer risk (LCR ≤ 10−5, safe) was determined to be 8.81 × 10−12–9.79 × 10−7. Based on the results of both risk assessments, the levels of unintentional phthalates contaminants in cosmetics were deemed safe. Some phthalates are widely used as plasticizers and are essential for daily life; however, various toxicities, including endocrine disruption, have been reported. Therefore, even under these “worst case” assumptions, an adequate margin of safety is shown such that this might be a low priority for further work although exposure to unintentional phthalates contaminants through cosmetics should be considered as part of cumulative exposure.

Risk assessment and hormone evaluation were carried out for di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), endocrine disrupting chemicals (EDCs), in 302 Korean children (n = 223) and adolescents (n = 79) ( age 19). Urinary and serum concentrations of DEHP, MEHP (mono(2-ethylhexyl) phthalate), DBP, MBP (monobutyl phthalate), and PA (phthalic acid, a common final metabolite of phthalates) were detected in children and adolescents. Daily exposure levels were estimated to be 16.45 ± 36.50 μg/kg b.w./day for DEHP, which is one-third of the tolerable daily intake (TDI) value (50 μg/kg b.w./day), but 14 out of 302 participants had a hazard index (HI = intake/TDI) value1. The mean daily exposure level of DBP was 1.23 ± 1.45 μg/kg b.w./day, which is one-eighth of the TDI value (10 μg/kg b.w./day), but 1 out of 302 participants had a HI value 1. Positive correlations were observed between serum DBP or MEHP, and serum estradiol (E2) and/or luteinizing hormone (LH) in prepubescent children. In addition, serum MBP levels were found to be negatively correlated with serum triiodothyronine (T3) or thyroxine (T4) in male participants, and serum DEHP levels with serum thyroid stimulating hormone (TSH) in female adolescents. Low-density lipoprotein (LDL) levels were positively correlated with serum PA levels in children and adolescents. DEHP, DBP or its metabolites may be associated with altered hormone levels in children and adolescents. Data suggest that exposure levels of DEHP and DBP in Korean children need to be reduced to levels below TDI to protect them from EDC-mediated toxicities. Abbreviations: DBP: dibutyl phthalate; DEHP: di(2-ethylhexyl) phthalate; E2: estradiol; EDC: endocrine disrupting chemical; EFSA: European Food Safety Authority; FSH: follicle stimulating hormone; HDL: high density lipoprotein; HI: hazard index; LDL: low density lipoprotein; LH: luteinizing hormone; MEHP: mono(2-ethylhexyl) phthalate; MBP: monobutyl phthalate; PA: phthalic acid; PPAR: peroxisome proliferator-activated receptor gamma; PVC: polyvinyl chloride; T3: triiodothyronine; T4: thyroxine; TDI: tolerable daily intake; TG: triglyceride; TSH: thyroid stimulating hormone; UPLC/MS/MS: Ultra Performance Liquid Chromatography/Tandem Mass Spectrometry; WWF: World Wildlife Fund.

The endocrine disrupting actions of di(2-ethylhexyl) phthalate (DEHP) on testicular functions are postulated to involve excess free radical generation. Thus the aim of this study was to examine the ability of antioxidant vitamins C and E to prevent DEHP-induced testicular disruption in male Sprague-Dawley (SD) rats. SD male rats were administered DEHP alone or DEHP with vitamin C and/or vitamin E for 30 days. DEHP alone increased the levels of testosterone (T) and reduced estradiol (E2) concentrations. Supplementation with antioxidant vitamins diminished or restored serum T levels noted in DEHP-treated rats to control values. In contrast vitamins C and E increased E2 levels to control in rats administered DEHP. Antioxidants significantly improved the decreased testicular levels of reduced glutathione and activity of superoxide dismutase compared to DEHP-treatment alone. Co-treatment of vitamins C and E also markedly improved the reduced epididymal sperm head counts and elevated levels of malondial...

The detoxifying effect of pyridoxine against acetaminophen (APAP)-induced hepatotoxicity was investigated. HepG2 cells were co-treated with APAP and pyridoxine to compare with betaine or methionine for 24 h. LDH, ALT and AST activities were measured to determine direct cells damage in vitro and in vivo. Lipid peroxidation, antioxidant enzymes activity, and glutathione level were measured. Cytochrome c releaseand procaspase-3, cleaved caspase-3, Bcl-2, or Bax protein levels were measured to determine APAP-induced apoptotic cell death. Pyridoxine treatment significantly increased cell viability and decreased leakage of LDH activity against APAP-induced hepatotoxicity in HepG2 cells. ALT and AST activities were dose-dependently reduced by pyridoxine treatment compared to APAP-treated group. Significant increases in activities of GST and GPx were observed after co-treatment with APAP and pyridoxine. Although APAP-induced Nrf2 and HO-1 expression levels were gradually reduced in HepG2 cells by pyridoxine treatment, induction of antioxidant enzymes activities were dose-dependently increased. These protected effects of pyridoxine against APAP-induced hepatoxicity were closely associated with suppression of APAP-induced oxidative stress and apoptotic cell death in HepG2 cells. These data indicated that the protective action of pyridoxine against hepatic cell injuries was involved in the direct antioxidant activity which provides a pivotal mechanism for its potential hepatoprotective action.

The heavy metal content of cosmetics may be a cause for concern in that exposure to these metals is associated with adverse consequences. Thus, the aim of this study was to assess consequences attributed to exposure to heavy metals in cosmetics as determined by non-cancer, cancer, and sensitization risks methodologies. The quantification and exposure assessments of aluminum (Al), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd), antimony (Sb), and titanium (Ti) were performed by inductively coupled plasma-mass spectrometry. The non-cancer risk assessment of Al, Cr

Dietary hydroxycinnamates are considered as attractive materials for radioprotection. This study explores whether hydroxycinnamates protect against γ-radiation-induced cellular damages and hematopoietic stem cell senescence. C57BL/6 mice were orally administered with each of caffeic acid, p-coumaric acid, and ferulic acid (20mg/kg body weight) once per three days for five times before exposure to total body radiation (5 Gy). Irradiation increased the activities of alanine amino transaminase and aspartate aminotransferase in blood serum but decreased the anti-oxidant defense enzyme activities in the liver and spleen tissues. Oral administration of the compounds almost completely prevented irradiation-mediated changes in these enzyme activities. The hydroxycinnamates also inhibited the irradiation-mediated increases in the mitochondrial superoxide anions of Lin−Sca-1+c-Kit+ (LSK) cells and CD150+CD48− LSK cells in the bone marrow. These results suggest that dietary hydroxycinnamates protect against irradiation-mediated oxidative damages of tissues and bone marrow progenitor cells.

Potential biomarkers of skin sensitization in RAW264.7 mouse macrophages were investigated as alternatives to animal experiments and risk assessment. The concentrations that resulted in a cell viability of 90% (CV90) and 75% (CV75) were calculated by using a water-soluble tetrazolium salt (WST)-1 assay and used to analyze the skin sensitization potency of 23 experimental materials under equivalent treatment conditions. In addition, the expression of interleukin (IL)-1α, IL-1β, IL-31, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2) was analyzed utilizing Western blotting. In the cell viability analysis, skin sensitizers were generally more cytotoxic and exhibited increased skin sensitization potency. However, nonsensitizers did not show any marked cytotoxic tendency. Biomarker analysis demonstrated that IL-1α, IL-1β, and the combination of IL-1α and IL-1β (IL-1α + IL-1β) predicted reliably skin sensitization potential (1) sensitivities of 94.4%, 83.3%, and 83.3%, specificities of 100%, 100%, and 100%, and (2) accuracies of 95.7%, 87%, and 87%, respectively. These observations correlated most reliably as indicators for skin sensitization potency. Data suggest that IL-1α and IL-1β may serve as potential biomarkers for skin sensitization and provide an alternative method to animal experiments for prediction of skin sensitization potency and risk assessment.

N-nitrosamines and their precursors found in cosmetics may be carcinogenic in humans. Thus the aim of this study was to carry out risk assessment for N-nitrosamines (N-nitrosodiethanolamine [NDELA], N-nitrosodiethylamine [NDEA]) and amines (triethanolamine [TEA], diethanolamine [DEA]) levels in cosmetics determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedures. NDELA and NDEA concentrations were present at levels of "not detected" (N.D.) to 596.5 μg/kg and N.D. to 40.9 μg/kg, respectively. TEA and DEA concentrations ranged from N.D. to 860 μg/kg and N.D. to 26.22 μg/kg, respectively. The nitrite concentration (3-2250 mg/l), number of nitrosating agents to a maximum 5, and pH (3.93-10.09) were also assessed. The impact of N-nitrosamine formation on the levels of TEA, DEA, nitrite, and other nitrosating agents was also examined. N-nitrosamine concentrations correlated with the number of nitrosating agents and nitrite concentrations. Data demonstrated that higher nitrite concentrations and a greater number of nitrosating agents increased NDELA and NDEA yields. Further, the presence of TEA and DEA exerted a significant influence on N-nitrosamine formation. Risk assessments, including the margin of exposure (MOE) and lifetime cancer risk (LCR) for N-nitrosamines and margin of safety (MOS) for amines, were calculated using product type, use pattern, and concentrations. Exposure to maximum amounts of NDELA and NDEA resulted in MOE 10,000 (based upon the benchmark dose lower confidence limit 10%) and LCR1 × 10

N-nitrosodiethanolamine (NDELA), a type of nitrosamine, is a possible human carcinogen that may form in cosmetic products. The aim of this study was to examine the formation and inhibition of NDELA through chemical reactions of secondary amines including mono-ethanolamine, di-ethanolamine (DEA), and tri-ethanolamine (TEA), and sodium nitrite (SN) under varying conditions such as pH, temperature, and fluorescent, ultraviolet (UV), and visual light (VIS) using liquid chromatography-mass spectroscopy. In a mixture of TEA and SN under acidic conditions pH 2, residual NDELA concentrations rose significantly under various storage conditions in the following order: 50°C 40°C UV (2 W/m

Background Concurrent endocrine therapy with chemotherapy had a concern of potential antagonism. However, gonadotropin-releasing hormone (GnRH) agonist has been used concurrently with chemotherapy to prevent premature ovarian failure for young breast cancer patients. The aim of this study was to determine the impact of concurrent use of GnRH agonists on relapse-free and overall survival, and to establish the oncologic safety of ovarian protection with GnRH agonists. Methods Premenopausal women aged between 20 and 40 years who received adjuvant chemotherapy for breast cancer from January 2002 to April 2012 were classified into two groups; One treated with GnRH agonists for ovarian protection during chemotherapy, and the other without ovarian protection. A propensity score matching strategy was used to create matched sets of two groups with age, pathologic stage, hormone receptor, and Her2 status. Results A total of 101 patients treated with concurrent GnRH agonist during chemotherapy were compared with 335 propensity score matched patients. Among them, 81.2% were younger than 35 years and 58.4% were hormone responsive. Survival analysis using stratified Cox regression showed that women treated with concurrent GnRH agonists had better recurrence-free survival (adjusted Hazard ratio 0.21, p = 0.009; unadjusted Hazard ratio 0.33, p = 0.034). Conclusions Ovarian protection using GnRH agonists can be safely considered for young women with breast cancer in terms of oncologic outcomes. Further studies are needed to assess the long-term outcomes of concurrent GnRH agonist use with chemotherapy.

PURPOSE Recently, through international marriage, immigrant women have rapidly increased throughout Korea. This study was performed to identify health beliefs and practices related to breast cancer screening in immigrant women in Korea. METHODS A cross-sectional survey was carried out between March and July 2012, and study population included immigrant females from six other Asian countries (Cambodia, China, Japan, Mongolia, Vietnam, and the Philippines). We surveyed 197 women and categorized them into four groups according to home countries. The questionnaire consisted of 55 items, including demographic and socioeconomic factors, breast cancer-related knowledge regarding risk factors and symptoms, beliefs and attitudes towards health and breast cancer, perceived susceptibility, barriers, and benefits of screening. RESULTS Japanese participants were significantly older and had resided in Korea for more years than other country-of-origin groups (all p

Glioma stem cells (GSCs) are presumably major culprits for brain tumor initiation, progression, and recurrence after conventional therapies. Thus, selective targeting and eradication of GSCs may provide a promising and effective therapeutic approach. Here, we isolated a GSC-targeting (GSCT) peptide that demonstrated selective binding affinity for many undifferentiated GSCs using in vitro phage display technology. This GSCT peptide binds to isotypes of Nestin proteins specifically expressed in GSCs, enabling it to target Nestin-positive cells in human glioblastoma tissues. In human glioblastoma tissue specimens, the fluorescence-conjugated GSCT peptide could visualize putative GSC populations, showing its possible use as a diagnostic agent. GSCT peptide is also internalized into undifferentiated GSCs specifically in vitro, and moreover, intravenously injected GSCT peptide effectively penetrated into tissues, specifically accumulated in gliomas that arise from subcutaneous and orthotopic implantation, and predominantly targeted Nestin-positive cells in these tumors. Thus, our GSCT peptide may be useful for the development of more promising therapeutic and diagnostic modalities that target GSCs in brain tumors.

The objective of this study was to determine the effect of feeding direct-fed microbials (DFM) on the growth performance and prophylaxis of calf diarrhea during the pre-weaning period as an alternative to antibiotics. A multi-species DFM was formulated including three lactic acid bacteria (Lactobacillus salivarius Ls29, Pediococcus acidilactia Pa175, and L. plantarum Lp177), three Bacillus strains (B. subtilis T4, B. polymyxa T1 and SM2), one yeast, Saccharomyces boulardii, and a nonpathogenic E. coli Nissle 1917. Lactic acid bacteria and Bacillus strains were selected based on the antibacterial activity against various animal pathogens, especially pathogenic E. coli using agar diffusion methods in vitro. Test and control groups were fed milk replacer and calf starter supplemented with DFM (10 9 cfu each of eight species/d/head, n = 29) or with antibiotics (0.1% neomycin sulfate in milk replacer and Colistin 0.08% and Oxyneo 110/110 0.1% in calf starter, n = 15), respectively. Overall fecal score and the incidence rate of diarrhea were reduced in the DFM group compared to the antibiotics one. About 40% of calves in antibiotic group suffered from diarrhea while in DFM group only 14% showed diarrhea. There was no difference in the average daily gain and feed efficiency of two groups. The hematological levels of calves were all within the normal range with no significant difference. In conclusion, the feeding of multi- species DFM during the pre-weaning period could reduce calf diarrhea and there was no difference in the growth performance between

To find novel targeting moieties to lactating mammary gland, in vivo phage display screening was conducted with lactating rats and a peptide ligand, CLHQHNQMC (designated as MG1), which specifically homes to the mammary tissue during lactation, was identified through the consecutive in vivo biopannings. MG1 peptide ligand showed specific binding affinity to lactating mammary tissue without any preference to other organs tested in ex vivo and in vivo validation, and microscopy analysis revealed that systemically introduced MG1 could be specifically localized in the lactating mammary gland associated with mammary epithelia and alveolar vasculature. Based on the observation that binding of MG1-encoding phage to lactating mammary gland was competitively inhibited by synthetic MG1 peptide ligand, we attempted to identify a counterpart molecule corresponding to specific recognition of the MG1 and the acidic Ribosomal Protein Large P0 (RPLP0) was selected as a candidate receptor for MG1 by peptide affinity pull-down assay with protein extracts from lactating mammary tissue. We demonstrated specific expression of RPLP0 in mammary tissue, especially during lactation, by immunoblotting assays and also demonstrated that MG1 peptide ligand could be bound to, and internalized into, the cells effectively via specific interaction with RPLP0 by analysis using an in vitro endothelial cell model. The overall results suggest that the MG1 has a specific affinity with RPLP0 which are dominantly expressed on the mammary vasculature during lactation and this specific affinity enables the MG1 would be served as an effective homing ligand to deliver functional molecules to the lactating mammary gland.

Ethnopharmacological relevance Water extract of Raphanus sativus L. (RSL) seeds was traditionally used to treat digestive inflammatory complaints in Korean culture. RSL seeds exerted antioxidant, anti-inflammatory, and anti-septic functions, suggesting their pharmacological potential for the treatment of inflammatory pathologies associated with oxidative stress such as inflammatory bowel disease. Aim of this study We evaluated the intestinal anti-inflammatory effects of RSL seed water extract (RWE) in experimental rat models of trinitrobenzenesulphonic acid (TNBS)- or dextran sodium sulfate (DSS)-induced colitis. Materials and methods RWE was characterized by determining the content of sinapic acid as a reference material and then assayed in the DSS and TNBS models of rat colitis. Male Sprague–Dawley rats were divided into 10 groups ( n =7/group): non-colitic control, DSS or TNBS control, DSS colitis groups treated with RWE (100 mg/kg) or mesalazine (25 mg/kg), and TNBS colitis groups treated with various doses (10, 40, 70, and 100 mg/kg) of RWE or mesalazine (25 mg/kg). RWE or mesalazine treatment started the same day of colitis induction and rats were sacrificed 24 h after the last treatment followed by histological and biochemical analyses. Results Oral administration with RWE suppressed intestinal inflammatory damages in both DSS- and TNBS-induced colitic rats. The treatment with 100 mg/kg RWE recovered intestinal damages caused by TNBS or DSS to levels similar to that of mesalazine, decreasing the activity of myeloperoxidase activity and the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. RWE treatment inhibited malondialdehyde production and glutathione reduction in colon of colitis rats. The administration of RWE at dose of 100 mg/kg also suppressed the TNBS- or DSS-stimulated expression of TNF-α , IL-1β , monocyte chemotactic protein-1 , inducible nitric oxide , and intercellular adhesion molecule-1 . Furthermore, RWE inhibited p38 kinase and DNA–nuclear factor-κB binding activities, both of which were stimulated in the colitic rats. Conclusions The current findings show that RWE ameliorates intestinal oxidative and inflammatory damages in DSS and TNBS models of rat colitis, suggesting its beneficial use for the treatment of intestinal inflammatory disorders.

Cadillac Mountain—the highest peak along the eastern seaboard of the United States—is a major tourist destination in Acadia National Park, Maine. Managing vegetation impact due to trampling on the Cadillac Mountain summit is extremely challenging because of the large number of visitors and the general open nature of landscape in this fragile subalpine environmental setting. Since 2000, more intensive management strategies—based on placing physical barriers and educational messages for visitors—have been employed to protect threatened vegetation, decrease vegetation impact, and enhance vegetation recovery in the vicinity of the summit loop trail. The primary purpose of this study was to evaluate the effect of the management strategies employed. For this purpose, vegetation cover changes between 2001 and 2007 were detected using multispectral high spatial resolution remote sensing data sets. A normalized difference vegetation index was employed to identify the rates of increase and decrease in the vegetation areas. Three buffering distances (30, 60, and 90 m) from the edges of the trail were used to define multiple spatial extents of the site, and the same spatial extents were employed at a nearby control site that had no visitors. No significant differences were detected between the mean rates of vegetation increase and decrease at the experimental site compared with a nearby control site in the case of a small spatial scale (≤30 m) comparison (in all cases P > 0.05). However, in the medium (≤60 m) and large (≤90 m) spatial scales, the rates of increased vegetation were significantly greater and rates of decreased vegetation significantly lower at the experimental site compared with the control site (in all cases P

In this study, we demonstrated that the CSKSSDYQC-peptide ligand which was identified from a random phage-peptide library through an in vivo phage display technique with rats could prominently improve the transport efficiency of macromolecules, such as large filamentous phage particles (M13 bacteriophage), across the intestinal mucosal barrier. Synthetic CSKSSDYQC-peptide ligands significantly inhibited the binding of phage P1 encoding CSKSSDYQC-peptide ligands to the intestinal mucosal tissue and immunohistochemical analysis showed that the CSKSSDYQC-peptide ligands could be transported across the intestinal mucosal barrier via goblet cells as their specific gateway. Thus, we inferred that CSKSSDYQC-peptide ligand might have a specific receptor on the goblet cells and transported from intestinal lumen to systemic circulation by transcytosis mechanism. These results suggest that CSKSSDYQC-ligand could be a promising tool for development of an efficient oral delivery system for macromolecular therapeutics in the carrier-drug conjugate strategy.

Background Oral delivery is a highly desirable property for candidate drugs under development. Computational modeling could provide a quick and inexpensive way to assess the intestinal permeability of a molecule. Although there have been several studies aimed at predicting the intestinal absorption of chemical compounds, there have been no attempts to predict intestinal permeability on the basis of peptide sequence information. To develop models for predicting the intestinal permeability of peptides, we adopted an artificial neural network as a machine-learning algorithm. The positive control data consisted of intestinal barrier-permeable peptides obtained by the peroral phage display technique, and the negative control data were prepared from random sequences. Results The capacity of our models to make appropriate predictions was validated by statistical indicators including sensitivity, specificity, enrichment curve, and the area under the receiver operating characteristic (ROC) curve (the ROC score). The training and test set statistics indicated that our models were of strikingly good quality and could discriminate between permeable and random sequences with a high level of confidence. Conclusion We developed artificial neural network models to predict the intestinal permeabilities of oligopeptides on the basis of peptide sequence information. Both binary and VHSE (principal components score V ectors of H ydrophobic, S teric and E lectronic properties) descriptors produced statistically significant training models; the models with simple neural network architectures showed slightly greater predictive power than those with complex ones. We anticipate that our models will be applicable to the selection of intestinal barrier-permeable peptides for generating peptide drugs or peptidomimetics.