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We developed a method to produce a soluble form of a single-chain fragment variable (scFv) targeting human epithelial growth factor receptor 2 (HER2) in Escherichia coli. By optimizing the orientations of the variable heavy (VH) and variable light (VL) domains and the His-tag, we identified the HL-His type antibody with the highest HER2-binding activity. Purification of HL-His yielded 40.7 mg from a 1 L culture, achieving >99% purity. The limit of detection was determined to be 2.9 ng, demonstrating high production yield, purity, and sensitivity. Moreover, we successfully labeled HER2 + cell lines with fluorescent dye-conjugated scFv, resulting in a significantly higher observed signal-to-background ratio, compared to that of HER2 - cell lines. This highlights the potential of these fluorescent scFvs as valuable probes for HER2 + breast cancer diagnostics. Notably, the process for the complete scFv production was streamlined and required only 4-5 days. Additionally, the product maintained its activity after freeze storage, allowing for large-scale production and a wide range of practical applications., (© 2024 The Author(s). Biotechnology Journal published by Wiley‐VCH GmbH.)

This study investigated the nitrate dual isotopic compositions (δ 15 N NO3 and δ 18 O NO3 ) of water samples to trace nitrate sources in Lake Sihwa, which encompasses various land-use types (e.g., urban, industry, wetland, and agriculture). The biogeochemical interactions of anthropogenic nitrogen sources (e.g., soil, road dust, and septic water) were also evaluated through multiple pathways from terrestrial boundaries to the water column. Based on increased concentrations of dissolved total nitrogen (DTN; 3.1 ± 1.6 mg/L) after typhoon, the variation of element stoichiometry (N:P:Si) in this system shifted to the relatively N-rich conditions (DIN/DIP; 14.1 ± 8.1, DIN/DSi; 1.4 ± 1.8), potentially triggering the occurrence of harmful algal blooms. Furthermore, discriminative isotopic compositions (δ 15 N NO3 ; 4.0 ± 2.1 ‰, δ 18 O NO3 ; 6.1 ± 4.3 ‰) after the typhoon suggested the increased DTN input of anthropogenic origins within Lake Sihwa would be mainly transported from urban sources (76 ± 9 %). Consequently, the isotopic-based approach may be useful for effective water quality management under increased anthropogenic activities near aquatic systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Large uncertainties exist regarding the combined effects of pollution and impoundment on riverine greenhouse gas (GHG) emissions. It has also been debated whether river eutrophication can transform downstream estuaries into carbon sinks. To assess human impacts on the riverine and estuarine distributions of CO 2 , CH 4 , and N 2 O, two source-to-estuary surveys along three impounded rivers in Korea were combined with multiple samplings at five or six estuarine sites. The basin-wide surveys revealed predominant pollution effects generating localized hotspots of riverine GHGs along metropolitan areas. The localized pollution effect was pronounced in the lower Han River and estuary adjacent to Seoul, while the highest GHG levels in the upper Yeongsan traversing Gwangju were not carried over into the faraway estuary. CH 4 levels were elevated across the eutrophic middle Nakdong reaches regulated by eight cascade weirs in contrast to undersaturated CO 2 indicating enhanced phytoplankton production. The levels of all three GHGs tended to be higher in the Han estuary across seasons. Higher summer-time δ 13 C-CH 4 values at some Nakdong and Yeongsan estuarine sites implied that temperature-enhanced CH 4 production may have been dampened by increased CH 4 oxidation. Our results suggest that the location and magnitude of pollution sources and impoundments control basin-specific longitudinal GHG distributions and estuarine carryover effects, warning against simple generalizations of eutrophic rivers and estuaries as carbon sinks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quantitative estimation for tracking the transport of various nitrate sources is required to effectively manage nitrate loading in complex river systems. In this study, we validated an integrated framework using field isotopic data (δ 15 N NO3 and δ 18 O NO3 ) of nitrates and hydrological modeling (hydrological simulation program FORTRAN; HSPF) to determine anthropogenic nitrate flux among different land-use types within a watershed. Nitrate isotopic compositions showed different ranges among four land-use types (4.9 to 15.5‰ for δ 15 N NO3 , -4.9 to 12.1‰ for δ 18 O NO3 ), reflecting the different nitrate sources (sewage, synthetic fertilizer, effluent and soil) within watersheds. Based on the integration of HSPF modeling, we also found that total nitrate loads might be partially controlled by hydrological conditions such as water discharge (12,040.3-22,793.2 L/s) from upstream to downstream. Among the nitrate sources, the sewage transport showed unique enhancement near urban boundaries, along with an increase in total nitrate load (>193.5 NO 3 -N g/s km 2 ) in downstream areas. In addition, the isotopic- and model-based nitrate fluxes showed good correlation for urban sources (R 2 =0.73, p < 0.05) but poor correlations for agriculture-dominated land use (R 2 =0.13, p > 0.05), reflecting the potential influence of surface runoff and ground infiltration into the watershed. Consequently, this research provided useful information to establish nitrogen management policy controlling point and non-point nitrate source loads in various land-use types for the restoration of water quality and aquatic ecosystem in the complex river system. Considering the recent increase in human activities near aquatic environments, this framework would be effective for individually estimating the quantitative contributions of anthropogenic nitrate sources transported along river-coastal systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Weight gain in adults is associated with an increased risk of obesity-related diseases and high healthcare costs. However, there have been limited studies on weight gain in Asians. This study investigated the prevalence, comorbidities, and associated factors of weight gain in the Korean population., Methods: This is a cross-sectional study of Korean adults aged 19-64 years who participated in the Korea National Health and Nutritional Examination Survey 2016-2019. We used data from 15,514 adults (subjects 1) to analyze the prevalence of weight gain. Finally, after excluding adults with suspicious debilitating conditions among them, 11,477 adults (subjects 2) were used to analyze comorbidities and associated factors. Weight changes and lifestyle factors were assessed using a self-report questionnaire. We analyzed odds ratios and 95% confidence intervals using multivariable logistic regression analysis to examine factors associated with weight gain., Results: The overall prevalence of weight gain was 25.7% in men and 31.3% in women and decreased significantly with age in both sexes. Weight gain of ≥ 6 kg was evident in 10.5% of men and 9.8% of women and was more pronounced with a higher baseline body mass index (BMI). Most metabolic comorbidities worsened the greater the weight gain. Young age was the strongest associated factor for weight gain. Other factors associated with weight gain were being unmarried, blue-collar job, lower income, and alcohol consumption in men; being married in women; smoking and skipping breakfast in both sexes., Conclusion: Weight gain was much more pronounced in younger adults and at a higher baseline BMI in both sexes. Public education and health policies to prevent unnecessary weight gain should be strengthened by considering the associated harmful factors in Korean adults., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

We investigated the composition, source, and reactivity of sedimentary organic matter (OM) present in aquaculture systems along the Korean coast. A multi-isotopic approach was applied to 216 surface sediments from five sections: western (W)-1, W-2, southern (S)-1, S-2, and eastern (E)-1 sections. The 15 N-enriched total nitrogen signatures in the surface sediments of the W-1 section may indicate that a substantial fraction of sedimentary OM has anthropogenic origins exported through the Han River. Simultaneously, the deposition of allochthonous OM is predominant in the S sections (Jinhae and Masan Bays). The 34 S-depleted patterns at the S-2 section may indicate that sulfate reduction occurring at the sedimentary boundary contributes to active OM decomposition, depending on the increased sedimentation of the aquaculture-derived OM. Our results highlight that isotopic-based source tracking near aquaculture systems provide important information for identifying anthropogenic contamination in coastal marine sediments and for improving environmental management., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

While there are many studies that have reported methods for tracing the geographical origin of seafoods, most of them have focused on identifying parameters that can be used effectively and not the direct application of these methods. In this study, we attempted to differentiate the geographical origins of the Manila clam R. philippinarum collected from different sites in Korea, the Democratic People's Republic of Korea, and China using a combination of analyses based on dual-element isotopes, fatty acids (FAs), and compound-specific isotopic analysis of FAs. We hypothesized that a stepwise application of new parameters to unclassified samples could achieve this objective by integrating new information while reducing time and labor. The FA profiles and compound-specific carbon isotopic values of FAs were found to enhance the discrimination power of determining the geographic origin up to 100%. Our findings demonstrate the advantageousness of using several parameters simultaneously over the conventional method of employing individual analytical methods when identifying geographic origins of the Manila clam, which could have implications for tracing the origins of different shellfish species or other food products as well.

A new town is strategically built within a short period compared to naturally developed cities. It is considered an appropriate study area for analyzing the urban climate problems such as surface urban heat islands (SUHIs) that is differently generated according to urban planning and development. In this study, we suggest comprehensive method for determining and comparing changes in surface UHI distribution during 1989-2048 in two new towns with different urban planning. First, a substantial increase in built-up areas was observed from 1989 (< 5%) to 2018 (> 40%) in both new towns. However, SUHI phenomenon-increasing patterns were different of about 12.25% depending on urban planning and urban morphology. Results also showed the importance of vertical and horizontal structures which can have a great influence on SUHI intensity and accordingly, the difference in SUHI distribution between two new towns was confirmed. Moreover, without effective mitigation, the built-up area in both new towns is estimated to increase to approximately 60%, and the SUHI intensity in most areas to increase by 4 °C in 2048. In addition, the spread and intensification of the SUHI phenomenon are predicted to be greater due to the characteristics of the building structure and the active urban expansion. Thus, these results combined with architectural assessment models can improve the understanding of thermal environmental impacts of urbanization and provide directions for sustainable urban development and renovation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Owing to the coronavirus disease 19 pandemic, the demand for telemedicine has increased. However, the awareness of and experience with telemedicine among the Korean population have not been investigated. Therefore, we examined Korean outpatients' experience with and awareness of telemedicine. Methods: From December 2020 to March 2021, we conducted a survey exploring the awareness of and experience with telemedicine of outpatients who were consecutively enrolled by family physicians from four hospitals. The participants completed questionnaires on sociodemographic characteristics and knowledge, experience, satisfaction, preference, and future considerations concerning telemedicine. We evaluated factors associated with satisfaction with telemedicine experiences using multivariate logistic regression analysis. Results: Among the 563 study participants, 364 participants had experience with telemedicine. More than 95% of the telemedicine visits were performed by telephone consultation, and the most common disease type for telemedicine visits was chronic diseases (67.5%). Overall, 82.4% of the participants were satisfied with telemedicine. More than 90% of the participants were satisfied with telemedicine in terms of saving time and money relative to hospital visits, no risk of infection, and convenience. According to the multivariate logistic regression analysis, adults aged ≥65 years (odds ratio [OR] 3.53, 95% confidence interval [CI] 1.44-8.68), residents of a metropolitan city (OR 6.8, 95% CI 1.41-32.55), and those with knowledge of telemedicine (OR 2.96, 95% CI 1.21-7.26) were more likely to be satisfied with their telemedicine experience, compared with their counterparts. For chronic diseases, participants with telemedicine experience were significantly more likely to prefer telemedicine for revisits, compared with those with no telemedicine experience. Nonetheless, most respondents recognized that telemedicine requires improvement. Conclusions: Most Korean outpatients showed high satisfaction with telemedicine. Telemedicine may be considered in various medical situations in the future. Therefore, building a practical system for telemedicine and changes in the medical environment are required.

Background: Obesity affects health-related quality of life (QoL); however, their relationship among elderly Asians is not well known., Aims: Relationship of domain-specific QoL with body mass index (BMI) and waist circumference and the sex differences were investigated using a nationally representative sample of elderly Korean population., Methods: In the Korea National Health and Nutrition Examination Survey phase VII (2016-2018), 3659 adults aged ≥ 65 years (1551 men and 2108 women) participated. BMI and waist circumference were classified according to Asian- and Korean-specific criteria. QoL was evaluated using the European Quality of Life Scale-Five Dimensions (EQ-5D). Multivariable logistic regressions were used to examine the relationship of QoL with BMI and waist circumference., Results: Men with BMI < 18.5 kg/m 2 and ≥ 25.0 kg/m 2 had a significant association with poor QoL in mobility and self-care, but no relationship was found with the other domains. Women with BMI ≥ 25.0 kg/m 2 had poor QoL in mobility and self-care, and those with BMI ≥ 30.0 kg/m 2 had poor QoL in usual activities and pain/discomfort. There was no significant association with anxiety/depression. Both elderly men and women with abdominal obesity had a significant association with poor QoL in mobility, self-care, usual activities, and pain/discomfort; however, there was no significant relationship with waist circumference and anxiety/depression., Conclusions: The association between QoL and BMI was different according to sex and the domains of QoL. Domain-specific QoL should be considered in the management of body weight of the elderly., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Understanding the development of early states on the Korean Peninsula is an important topic in Korean archaeology. However, it is not clear how social structure was organized by these early states and what natural resources were utilized from their surrounding environments. To investigate dietary adaptation and social status in ancient Korea, stable isotope ratios and radiocarbon dates were measured from humans and animals from the Imdang cemetery, Gyeongsan city, South Korea. The results indicate that the Imdang diet was mainly based on C 3 plants and terrestrial animals. Animal remains in the graves were directly consumed as daily food items as well as for ritual offerings. MixSIAR modeling results revealed that the dietary sources for the humans were: game birds > C 3 plants > terrestrial herbivores > marine fish > C 4 plants. The finding that the game birds represented the highest contribution to the whole diet, indicates that game birds must have been intensively hunted. Furthermore, elites consumed more game birds than their retainers and they also consumed seafood as a privileged dietary item in the Imdang society. This study demonstrates that the Apdok was a stratified society having high variations in the consumption of food items available to an individual and provides new insights about the subsistence and social status of the early ancient Apdok state on the Korean Peninsula., (© 2021. The Author(s).)

In this study, we used stable isotope-labeled soluble microbial products (SMP) and substrates to explore their assimilation into the formation of new biological products (i.e., extracellular polymeric substances and biomass) in two adjacent sequencing batch reactors. The isotope labeling approach along with fluorescence spectroscopy allowed us to distinguish between refractory and labile portions of SMP constituents as well as their roles in the formation of extracellular polymeric substances (EPS). Comparison of SMP fluorescence and the specific UV absorbance values between the two reactors revealed the presence of humic-like aromatic substances in the non-consumable part of SMP, which can be ultimately released as effluent organic matter. Parallel factor analysis modeling of fluorescence spectra showed that the hydrolysis of EPS contents mostly resulted in humic-like components in SMP rather than protein-like components, which were initially abundant in EPS (>80%). From variations in carbon and nitrogen isotopic contents in EPS and biomass, it was found that carbon-containing substrates were enriched faster than their nitrogenous counterparts. The contributions to new EPS formation reached 87.5% for carbon and 60.5% for nitrogen. Meanwhile, the isotopic tracking of the labeled SMP revealed that only 11.0% and 11.9% of carbon and 13.3% and 11.6% of nitrogen from the influent SMP were finally assimilated into EPS and biomass, respectively. In contrast, the isotopic enrichment in SMP was higher (~50%) than that of EPS and biomass, indicating the low bioavailability and refractory nature of the feed SMP. This study proposed a promising approach for estimating the relative contributions of different forms of labile substrate and SMP to the formation of EPS in activated sludge processes. This approach could be suggested as a versatile method for establishing the kinetics, substrate element flow, mass balance on organic substrates and nutrients, as well as for tracking the consumption and uptake pathways of hazardous materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite receiving a considerable amount of attention in the past, quantitative and systematic estimation of the source contributions for different organic carbons (OCs) in complex river systems is still challenging. In this study, we tested an integrated framework using field data of bulk elements and lipid biomarkers and hydrological modeling (hydrological simulation program FORTRAN, HSPF) for the quantitative estimation of OC loads along different land-use types of a watershed (Geumho River watershed in South Korea). Based on the specific source assignments identified from the lipid biomarker patterns in particulate organic carbon (POC) such as short/long chains of alkanes, fatty acids and alcohols, and coprostanol/cholesterol, spatial variations of the diagnostic lipids could be used as an indicator to discriminate between the contributions of natural (algae, bacteria, and terrestrial plants) and anthropogenic sources (fecal). Based on the integration of HSPF modeling, it was also found that various POC loads might be partially controlled by different water discharges within watersheds. With the increase in POC fluxes, the increase in fecal loads was also noticed, as reflected by the predominant lipid (especially coprostanol normalized by water discharges). As a straightforward approach, we developed a set of indices including fecal index-1, ratios of coprostanol, fatty acids, and alkanes, which strengthened the sensitivity for fecal contamination. Compared with the conventional HSPF results, the variations of these proposed indices were more influenced by the broadened watershed extents with increasing downstream distance, which provided a more accurate estimation of the quantitative contributions of POC loadings in the complex river system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The increasing global consumption of seafood has led to increased trade among nations, accompanied by mislabeling and fraudulent practices that have rendered authentication crucial. The multi-isotope ratio analysis is considered as applicable tool for evaluating geographical authentications but requires information and experience to select target elements such as isotopes, through a distinction method based on differences in habitat and physiology due to origin. The present study examined recombination conditions of multi-elements that facilitated geographically distinct classifications of the clams to sort out appropriate elements. Briefly, linear discriminant analysis (LDA) analysis was performed according to several combinations of five stable isotopes (carbon (δ 13 C), nitrogen (δ 15 N), oxygen (δ 18 O), hydrogen (δD), and sulfur (δ 34 S)) and two radiogenic elements (strontium ( 87 Sr/ 86 Sr) and neodymium ( 143 Nd/ 144 Nd)), and the geographical classification results of the Manila clam Ruditapes philippinarum from Democratic People's Republic of Korea (DPR Korea), Korea and China were compared. In conclusion, linear discriminant analysis (LDA) with at least four elements (C, N, O, and S) including S revealed a remarkable cluster distribution of the clams. These findings expanded the application of systematic multi-elements analyses, including stable and radiogenic isotopes, to trace the origins of R. philippinarum collected from the Korea, China, and DPR Korea.

Although various two-dimensional (2D) materials hold great promise in next generation electronic devices, there are many challenges to overcome to be used in practical applications. One of them is the substrate effect, which directly affects the device performance. The large interfacial area and interaction between 2D materials and substrate significantly deteriorate the device performance. Several top-down approaches have been suggested to solve the problem. Unfortunately, however, they have some drawbacks such as a complicated fabrication process, a high production cost, or a poor mechanical property. Here, we suggest the partially suspended 2D materials-based field-effect transistors (FETs) by introducing block copolymer (BCP) lithography to fabricate the substrate effect-free 2D electronic devices. A wide range of nanometer size holes (diameter = 31~43 nm) is successfully realized with a BCP self-assembly nanopatterning process. With this approach, the interaction mechanism between active 2D materials and substrate is elucidated by precisely measuring the device performance at varied feature size. Our strategy can be widely applied to fabricate 2D materials-based high performance electronic, optoelectronic, and energy devices using a versatile self-assembly nanopatterning process.

Background: Dyslipidemia is considered an independent health risk factor of cardiovascular disease (CVD), a leading cause of mortality in older adults. Despite its importance, there have been few reports on the association between lipoprotein cholesterol and future CVD and cardiovascular (CV) mortality among elderly Asians aged ≥ 65 years. This study investigated the association between lipoprotein cholesterol and future CVD and CV mortality in an elderly Korean population using a large nationwide sample., Methods: From the cohort database of the Korean National Health Insurance Service, 62,604 adults aged ≥ 65 years (32,584 men and 30,020 women) were included. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were categorized by quartiles. Cox proportional hazard models and linear regression analyses were used to assess the association between the quartiles of lipoprotein cholesterol and future CV events or mortality., Results: The mean follow-up period was 3.3 years. The incidence rates of ischemic heart disease and ischemic brain disease were 0.97 and 0.61 per 1,000 person-years, respectively, and the mortality rates from these diseases were 0.22 and 0.34 per 1,000 person-years, respectively. In a completely adjusted model, high HDL-C and LDL-C levels were not associated with total CV events and CVD mortality. However, high LDL-C levels were significantly associated with a lower incidence of ischemic brain disease. Furthermore, diabetic patients with high LDL-C levels were more likely to have higher CV mortality, whereas non-smokers with high LDL-C levels were less likely to be at risk of CV events., Conclusions: Neither high LDL-C nor HDL-C levels were significantly associated with future CV mortality in older adults aged ≥ 65 years. High LDL-C levels do not seem to be a risk factor for CVD in elderly individuals, and further studies are required.

Heated tobacco products (HTPs) have been widely used in Korea since their introduction in 2017. In this study, we investigated the perceptions of their relative harmfulness and smoking cessation effects. We performed an online survey in 7000 Koreans in 2018 (2300 males and 4700 females aged 20-69 years) by matching their age, sex, and provincial distribution. To investigate the factors causing HTPs to be perceived as less harmful than combustible cigarettes (CCs) and helpful for smoking cessation, we used multivariable logistic regression analyses. HTPs were less harmful than CCs in 16.8% of participants, particularly among HTP-only users and dual and triple users of HTPs, electronic cigarettes (ECs), or CCs than among CC-only users, those who were aged ≤ 34 years, males, and those with higher incomes. HTPs were reportedly helpful for smoking cessation in 11.2% of participants. Similar perceptions were more likely among HTP-only users, as well as dual and triple users than among CC-only users and adults with higher education/incomes. Although Korean adults generally had negative perceptions of the harmfulness and smoking cessation effects of HTPs compared with CCs, dual and triple users were more likely to have positive perceptions. Monitoring the use of multiple tobacco products and HTPs is a new challenge for Korean policymakers.

This study aimed to examine the association between disability and cardiovascular (CV) disease incidence and mortality in Korea longitudinally, using a national representative sample. We used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database, which includes information on the disability of the National Screening Program participants such as severity and type of disability, which were obtained from the Korean National Disability Registry. Cox proportional hazard models were used to evaluate the association between disability and CV disease incidence and mortality. We constructed four models with different levels of adjustment, in which Model 3 was a fully adjusted model. This study included 514,679 participants, and 7,317 CV deaths were reported within a mean follow up of 10.8 ± 3.9 years (maximum, 13.9 years). For 5,572,130 person-year (PY) follow-up, the CV mortality rate was 1.313 per 1,000 PY. In Models 1 and 2, CV disease incidence was significantly higher in participants with disability than in those without disability. In Model 3, the incidence was higher only among participants aged 50-64 years and severe disabled participants aged <50 years. CV mortality was significantly higher in participants with disability than in those without disability in all Models, and the mortality increased in both sexes in Models 1 and 2 but only increased in men in Model 3. Similar results were observed in the subgroup analysis of health behavior and chronic diseases. People with disability showed higher CV disease incidence and mortality than those without disability, regardless of the type of disability or risk factors for CV disease., Competing Interests: The authors have declared that no competing interests exist.

Inflammation is a defense response of the body to stimuli. Curly dock (CD) is an herbal food with anti-inflammatory effects. Beopje is an herbal food processing method that reduces toxicity and enhances beneficial effects. This study investigated the effects of CD and Beopje curly dock (CD-B) extracts on lipopolysaccharide (LPS)-induced inflammatory damage in RAW 264.7 cells. Cell survival rate and nitrite concentration were determined using the MTT assay and Griess method, respectively. Enzyme-linked immunosorbent assay was used to detect the inflammatory cytokine levels. The mRNA and protein expression levels of inflammatory associated genes were detected by qPCR and Western blot, respectively. CD and CD-B extracts compositions were assessed by UPLC-Q-TOF MS analysis. Our results indicate that CD-B has a more significant inhibitory effect on the LPS-induced inflammatory response in RAW 264.7 cells than CD, suggesting that the Beopje process potentially enhances the anti-inflammatory effect of CD. PRACTICAL APPLICATIONS: Long-term inflammation can cause a variety of chronic diseases. Therefore, it is necessary to suppress the occurrence of body inflammation in time. This study preliminarily clarified the mechanism of herbal foods to alleviate inflammation by regulating the immune response, and further confirms that applying the Beopje process enhances the anti-inflammatory effect. This research can serve as a significant reference for future research, prevention and treatment of inflammation-related diseases, and the development of functional foods with anti-inflammatory activity. It also provides a theoretical basis for the further reasonable application of Beopje processing method., (© 2020 Wiley Periodicals LLC.)

Background: Sea mustards are traditionally consumed as human food in many Asian countries. However, owing to the large consumption of seaweed, there are a substantial number of by-products produced during processing. These by-products after fermentation can provide a good alternative nutrient source for broilers and serve as a recycled resource reducing the environmental pollution of the seaweed industry. Therefore, an experiment was conducted to evaluate the effect of fermented sea mustard by-product (FSM) supplementation on growth performance, nutrient digestibility, excreta microflora, blood profiles, relative organ weight, and meat quality in broilers. The treatments were: control (CON), basal diet; FSM, CON +2 g kg -1 FSM., Results: During days 1 to 35, with the supplementation of 2 g kg -1 FSM, body weight gain (BWG) increased (P < 0.05), whereas the feed conversion ratio (FCR) decreased (P < 0.05). On day 35, with the supplementation of 2 g kg -1 FSM, excreta Lactobacillus counts increased (P < 0.05), and the excreta Escherichia coli counts decreased (P < 0.05). There were no significant effects (P > 0.05) on nutrient digestibility, blood profile, relative organ weight, and breast meat quality of broilers fed with FSM diets., Conclusion: Dietary supplementation of 2 g kg -1 FSM can improve growth performance, and shifted excreta microflora by increasing the proliferation of Lactobacillus counts and by decreasing E. coli counts. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Interactions between the ectodermal and mesenchymal tissues are the basis of the central mechanism regulating tooth development. Based on this epithelial-mesenchymal interaction (EMI), we demonstrated that copine-7 (CPNE7) is secreted by preameloblasts and regulates the differentiation of mesenchymal cells of dental or non-dental origin into odontoblasts. However, the precise expression patterns of CPNE7 in the stages of tooth development have not yet been elucidated. The aim of the present study was to establish the spatiotemporal expression pattern of CPNE7 during mouse tooth development. To examine the spatiotemporal expression patterns of CPNE7 during mouse tooth development, we investigate the distribution of CPNE7 in the embryonic and postnatal developing mouse tooth. Immunohistochemistry, in situ hybridization, real-time PCR, and western blot analysis are performed to investigate the CPNE7 expression pattern during tooth development of the mandibular mouse first molar. During the initiation stage (bud stage), CPNE7 protein expression is observed in the dental epithelium but not yet in the dental mesenchyme. At E18 (bell stage), expression of CPNE7 protein and mRNA is primarily observed in ectomesenchymal cells of dental papilla. At P7 (crown formation stage), CPNE7 is localized in differentiating odontoblasts but weak expression is detected in mature ameloblasts. These findings suggest that CPNE7 secreted by dental epithelium induces the differentiation of ectomesenchymal cells into preodontoblast in concert with EMI. CPNE7 is clearly expressed in differentiating odontoblasts and the odontoblast process during dentinogenesis, but is no longer expressed in fully differentiated odontoblasts. Furthermore, CPNE7 is expressed in the Hertwig's epithelial root sheath (HERS) and in the facing preodontoblasts during root dentin formation. Taken together, these results illustrate the dynamic expression of CPNE7 during tooth development and suggest its important function in entire stages of tooth development.

Rumex crispus (Rc) and Cordyceps militaris (Cm) mixture (Rc-Cm; AST2017-01) ameliorated production of proinflammatory cytokines, inflammation-related genes, and nitric oxide (NO) induced by lipopolysaccharide (LPS) in mouse splenocytes. Rc-Cm (6:4) and Taemyeongcheong (commercial healthy drink containing Rc-Cm) were co-administered along with LPS. Rc-Cm inhibited production of tumor necrosis factor α, interferon γ, interleukin (IL)-1β, and IL-6 in LPS-induced splenocytes. However, levels of inflammatory cytokines were elevated in the absence of LPS treatment. Rc-Cm significantly suppressed mRNA expression of IL-1β, IL-6, and the inflammation-related genes inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2), as well as NO production upon LPS co-treatment. Whereas Rc-Cm increased mRNA expression of IL-1β, and IL-6, but did not up-regulate expression of iNOS and COX-2, or increase NO production without LPS co-treatment. Therefore, treatment of Rc-Cm to LPS-induced splenocytes ameliorated induction of pro-inflammatory cytokines, inflammation-related genes, and NO production. In the absence of LPS, Rc-Cm treatment up-regulated pro-inflammatory cytokines but did not alter expression of the inflammation-related genes iNOS and COX-2 or NO production. These results indicate that the natural phytochemicals chrysophanol and cordycepin in Rc-Cm promote anti-inflammatory activities and immune cell responses., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest.

Coptis chinensis (CC) is used in conventional Chinese medicine. The main active components of CC are isoquinoline alkaloids, including berberine, coptisine, palmatine, and magnoflorine; all these are known to have several pharmacological properties. Poly(vinyl alcohol) (PVA) is a well-known synthetic biocompatible polymer suitable for a range of pharmaceutical uses; it can be used as a matrix for the incorporation of functional materials and has a wide range of applications in the cosmetics, food, pharmaceutical, and packaging industries. In this study, PVA-based electrospun nanofibers containing CC extract were successfully fabricated. Furthermore, the effects of different CC extract contents on the morphologies, and antimicrobial and antifungal properties of PVA/CC extract nanofibers were investigated. Morphological changes were observed using different molecular weights of PVA. For characterization, field-emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared analysis were performed. The effectiveness of these nanofibers has been demonstrated by evaluating the thermal stability against Staphylococcus aureus , antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis , and the antifungal activity against the fungi Aureobasidium pullulans and Penicillium pinophilum . The PVA/CC extract nanofibers were found to have excellent antibacterial and antifungal activity and thermal stability; hence, their use in medicinal sectors is highly recommended.

The present study investigated the anti-aging effects of pomegranate juice concentrated powder (PCP) in hairless mice following 15 weeks of UVB irradiation (three times a week; 0.18 J/cm 2 ). Skin moisturizing effects were evaluated through skin water, collagen type I and hyaluronan contents, as well as collagen type I and hyaluronan synthesis-related transcript levels. Wrinkle formation and edema scores (skin weights) were also assessed, along with skin matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13 transcript levels. To determine the anti-inflammatory effects of PCP, myeloperoxidase (MPO) activity, interleukin (IL)-1β and IL-10 contents were observed. Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) were used as an apoptotic index in epidermal keratinocytes. To determine the anti-oxidative effects of PCP, nitrotyrosine and 4-hydroxynonenal immunoreactive cells were detected and glutathione (GSH) content, malondialdehyde levels, superoxide anion production, Nox2, and GSH reductase mRNA expression were all measured. The results indicated that skin wrinkles induced by photoaging were significantly reduced by PCP, whereas skin water contents, collagen type I and hyaluronan contents all increased. Furthermore, IL-1β levels in the PCP-treated groups were lower than those in the UVB-exposed control group. UVB-induced GSH depletion was also inhibited by PCP. Taken together, the results of the current study suggest that PCP has favorable protective effects against UVB-induced photoaging through anti-apoptotic effects, MMP activity inhibition and ECM (COL1 and hyaluronan) synthesis-related moisturizing, anti-inflammatory and anti-oxidative effects.

In the present study, the complex anti-climacterium potential of standardized pomegranate concentrated solution (PCS) was investigated using bilateral ovariectomy (OVX) female ddY mice. Changes in body weight and gain during experimental periods, food consumption, serum estradiol levels, total body and abdominal fat densities, abdominal fat pads, and uterus weights were observed, along with the histopathology of abdominal fat pads and uterus for anti-obesity and estrogenic effects. In addition, liver weights, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and histopathological inspections were performed to explore the hepato-protective effects. Serum total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein, and triglyceride (TG) levels were monitored for hypolipidemic effects with total body and femur mean bone mineral density (BMD), right femur wet, dry and ash weights, strength, serum osteocalcin, bone-specific alkaline phosphatase (bALP) contents, and histological and histomorphometrical analyses for anti-osteoporosis activity. As a result of OVX, notable increases in body weight and gains, food consumption, abdominal fat mass densities, weights of abdominal fat pads deposited in the abdominal cavity, and serum AST, ALT, TC, LDL, TG, and osteocalcin levels were observed, along with decreases in the uterus, liver, and femur weights, mean total body and femur BMD, femur strength, serum bALP, and estradiol levels. In addition, marked hypertrophic alterations in adipocytes located in the deposited abdominal fat pads, liver steatosis, uterine disused atrophic changes, and decreases in bone mass and structures of the femur were also observed in OVX control mice with significant increases in bone resorption markers based on histopathological and histomorphometrical analysis. However, these estrogen-deficient climacterium symptoms were significantly (P<0.05 or P<0.01) inhibited after 84 days of continuous treatment with estradiol and PCS (1, 2 and 4 ml/kg), respectively. The present results suggested that PCS was able to effectively inhibit or refine the climacterium symptoms, including obesity, hyperlipidemia, hepatic steatosis, and osteoporosis, induced by OVX in ddY mice.

This study aimed to ascertain the optimal range of red clover dry extracts (RC) and dried pomegranate concentrate powder (PCP) to induce anti-climacteric effects. Thus, the dose ranges showing protective effect of mixed formulae consisting of RC and PCP were examined in ovariectomized mice. At 28 days after bilateral ovariectomy (OVX), mixed herbal compositions (RC:PCP = 1:1, 1:2, 1:4, 1:8, 2:1, 4:1, and 8:1) were administered orally, at 120 mg/kg once daily for 84 days. We evaluated that RC and PCP mixture attenuate OVX-caused obesity, hyperlipidemia, hepatic steatosis, and osteoporosis. Compared to OVX-induced control mice, body weight and abdominal fat weight in OVX-induced mice were significantly decreased, concomitantly with increase of uterus weight by RC:PCP mixture. Additionally, significant increases in serum estradiol levels were observed in all RC:PCP-treated mice. RC:PCP mixture also showed protective effect against OVX-induced hyperlipidemia, hepatic steatosis. Total body and femur mean bone mineral density (BMD), osteocalcin, bALP contents were effectively increased by RC:PCP mixture. Taken together, RC:PCP mixture (2:1, 1:1, and 4:1) has remarkable protective effects against the changes induced by OVX. In particular, RC:PCP mixture (2:1) shows the strongest effect and may be considered as a potential protective agent against climacteric symptoms.

Models that predict the timing of deciduous tree leaf emergence are typically very sensitive to temperature. However, many temperature data products, including those from climate models, have been developed at a very coarse spatial resolution. Such coarse-resolution temperature products can lead to highly biased predictions of leaf emergence. This study investigates how dynamical downscaling of climate models impacts simulations of deciduous tree leaf emergence in California. Models for leaf emergence are forced with temperatures simulated by a general circulation model (GCM) at ~200-km resolution for 1981-2000 and 2031-2050 conditions. GCM simulations are then dynamically downscaled to 32- and 8-km resolution, and leaf emergence is again simulated. For 1981-2000, the regional average leaf emergence date is 30.8 days earlier in 32-km simulations than in ~200-km simulations. Differences between the 32 and 8 km simulations are small and mostly local. The impact of downscaling from 200 to 8 km is ~15 % smaller in 2031-2050 than in 1981-2000, indicating that the impacts of downscaling are unlikely to be stationary.

The aim of the present study was to determine whether hexabromocyclododecane (HBCD) or 4-nonylphenol (NP) may induce prostatic cancer progression in LNCaP cells. Androgenic effects of HBCD and NP were examined in LNCaP prostate cancer cells expressing androgen receptors (ARs). HBCD and NP increased LNCaP cell viability similar to dihydrotestosterone (DHT) by MTT assay. This phenomenon was reversed by treatment with Casodex, an AR antagonist, suggesting that they act as xenoandrogens via AR signaling pathway. In cell migration assay, HBCD and NP also enhanced LNCaP cell migration similar to DHT. To elucidate underlying mechanisms of their actions on LNCaP, transcriptional levels of cell cycle- and apoptosis-related markers, including cyclin D1, cyclin E, p27, bcl-2, and bax, were determined by reverse transcription (RT)-PCR. An increase in expression cyclin D1 and cyclin E and reduction in p27 and bax mRNA levels were observed by their treatments. Western blot assay showed their alterations in translational levels of cyclin D1, cyclin E, p21, bax, and cathepsin D. Expressions of genes related to a G1/S transition of cell cycle and cathepsin D were elevated, while expression of p21 and bax was decreased. Taken together, these results indicate that HBCD and NP may enhance progression of prostate cancer by modulating growth and migration of LNCaP prostate cells by acting on cell cycle, apoptosis, and metastasis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

As a phytoestrogen, kaempferol (Kaem) is one of bioflavonoids, which are found in a variety of vegetables including broccoli, tea and tomato. In this study, the antiproliferative effects of Kaem in triclosn (TCS)-induced cell growth were examined in MCF-7 breast cancer cells. TCS promoted the cell viability of MCF-7 cells via estrogen receptor α (ERα) as did 17β-estradiol (E2), a positive control. On the other hand, Kaem significantly suppressed E2 or TCS-induced cell growth. To elucidate the molecular mechanisms of TCS and Kaem, alterations in the expressions of cell cycle, apoptosis and metastasis-related genes were identified using western blot assay. The treatment of the cells with TCS up-regulated the protein expressions of cyclin D1, cyclin E and cathepsin D, while down-regulated p21 and bax expressions. Kaem reversed TCS-induced gene expressions in an opposite manner. The phosphorylation of IRS-1, AKT, MEK1/2 and ERK was increased by TCS, indicating that TCS induced MCF-7 cell proliferation via nongenomic ER signaling pathway associated with IGF-1R. Kaem presented an antagonistic activity on this signaling by down-regulating the protein expression of pIRS-1, pAkt and pMEK1/2 promoted by E2 or TCS. In an in vivo xenografted mouse model, tumor growth was induced by treatment with E2 or TCS, which was identified in the measurement of tumor volume, hematoxylin and eosin staining, bromodeoxyuridine and immunohistochemistry assay. On the contrary, E2 or TCS-induced breast tumor growth was inhibited by co-treatment with Kaem, which is consistent with in vitro results. Taken together, these results revealed that Kaem has an anticancer effect against procancer activity of E2 or TCS, a xenoestrogen, in breast cancer and may be suggested as a prominent agent to neutralize breast cancer risk caused by TCS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Plants rich in antioxidant substances may be useful for preventing skin aging. Pomegranates, containing flavonoids and other polyphenolic compounds, are widely consumed due to their beneficial properties. We examined the underlying mechanisms of dried pomegranate concentrate powder (PCP) on melanin synthesis in B16F10 melanoma cells. The antioxidant effects of PCP were determined by measuring free radical scavenging capacity and transcript levels of antioxidant enzymes. To explore the inhibitory effects of PCP on melanin synthesis, we measured tyrosinase activity and melanin content in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. In addition, the levels of tyrosinase-related protein-1 (TRP-1), TRP-2, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression were determined by Western blotting. Changes in the phosphorylation status of protein kinase A (PKA), cAMP response element-binding protein (CREB), mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase Akt, and glycogen kinase 3β (GSK3β) were also examined. The free radical scavenging activity of PCP increased in a dose-dependent manner. In PCP-treated B16F10 cells, transcript levels of glutathione peroxidase-1 (GPx-1) were increased compared with α-MSH-stimulated cells. In addition, PCP led to the down-regulation of phospho-p38, phospho-PKA, phospho-CREB, phospho-GSK3β, MITF, and TRP-1 compared with α-MSH-stimulated B16F10 cells. We believe this effect may be associated with PCP activity, which leads to the inhibition of melanin production and tyrosinase activity. These results suggest that PCP decreases tyrosinase activity and melanin production via inactivation of the p38 and PKA signaling pathways, and subsequently decreases phosphorylation of CREB, MITF, and melanogenic enzymes. These observations provided new insights on the molecular mechanisms of the skin-whitening property of PCP.

Coastal lands and nearshore marine areas are productive and rapidly changing places. However, these areas face many environmental challenges related to climate change and human-induced impacts. Space-borne remote sensing systems may be restricted in monitoring these areas because of their spatial and temporal resolutions. In situ measurements are also constrained from accessing the area and obtaining wide-coverage data. In these respects, airborne remote sensing sensors could be the most appropriate tools for monitoring these coastal areas. In this study, a cost-effective airborne remote sensing system with synthetic aperture radar and thermal infrared sensors was implemented to survey coastal areas. Calibration techniques and geophysical model algorithms were developed for the airborne system to observe the topography of intertidal flats, coastal sea surface current, sea surface temperature, and submarine groundwater discharge.

Synopsis Botanical antioxidants have attracted much attention as useful preventatives of skin damage. Pomegranate is consumed throughout the world for its beneficial health effects, including its antioxidant and anti-inflammatory activities. We investigated whether pomegranate concentrated solution (PCS) could serve as a potential functional cosmetic ingredient that exerts a skin-whitening effect and antiwrinkle activity. To investigate the moisturizing effect of PCS, hyaluronidase activity was examined in human keratinocytes (HaCaT). Elastase and procollagenase activities were assessed in normal human primary dermal fibroblast-neonatal (HDF-N) cells to determine their antiwrinkle effects. Metalloproteinase 1 (MMP-1) activity was also assessed following ultraviolet A (UVA) irradiation. Whitening effects were measured by a tyrosinase inhibition assay and melanin formation test in mouse melanocytes (Melan-a). In addition, histopathological analysis was performed to determine the number of microfolds formed on the epithelial surface, mean epithelial thickness, mean number of inflammatory cells infiltrating the dermis, and collagen fiber-occupied regions within the dermis. Hyaluronan synthesis was significantly increased by PCS in HaCaT cells, while procollagenase and elastase activities were decreased in HDF-N cells. A significant decrease in UVA-induced MMP-1 activity was also observed in PCS-treated HDF-N cells, compared with UVA-exposed cells. PCS effectively reduced melanin production and mushroom tyrosinase activity in Melan-a cells. Moreover, UVB-induced histopathological dermal sclerosis and inflammatory signs were significantly attenuated in PCS-administered mice compared with UVB-exposed mice. Conclusions: Our results suggest that PCS prevents signs of aging, including those related to photoaging. These effects are associated with enhanced hyaluronan synthesis, as well as suppressed elastase, collagenase, MMP-1, and tyrosinase activities and melanin production. UVB-induced photoaging, such as histopathological dermal sclerosis and inflammatory signs, were effectively reduced on the addition of PCS. These results also suggest that skin aging can be prevented and reduced by the antioxidant effects of PCS.

Red clover (RC) shows potential activity against menopausal symptoms and pomegranates have antioxidative and beneficial effects on postmenopausal symptoms; thus, we investigated whether the anti-climacteric activity of RC could be enhanced by the addition of dried pomegranate concentrate powder (PCP) extracts in ovariectomized (OVX) rats. Regarding the anti-osteoporotic effects, bone mineral density increased significantly in OVX induced rats treated with 60 and 120 mg/kg of an RC:PCP 2:1 mixture, respectively, compared with OVX control rats. Additionally, femoral, tibia, and L4 bone resorption was decreased in OVX induced control rats treated with the RC:PCP 2:1 mixture (60 and 120 mg/kg), respectively, compared with OVX control rats. Regarding anti-obesity effects, the OVX induced rats treated with 60 and 120 mg/kg of the RC:PCP 2:1 mixture showed a decrease in total fat pad thickness, the mean diameters of adipocytes and the body weights gain compared with OVX induced control rats. The estradiol and bone-specific alkaline phosphatase levels were significantly increased in OVX induced rats treated with the RC:PCP 2:1 mixture (120 mg/kg) compared with OVX induced control rats, also, the uterine atrophy was significantly inhibited in 60 and 120 mg/kg of the RC:PCP 2:1 mixture treatment compared with OVX control rats. In conclusion, our results indicate that PCP enhanced the anti-climacteric effects of RC in OVX rats. The RC:PCP 2:1 mixture used in this study may be a promising new potent and protective agent for relieving climacteric symptoms.

Single radial immunodiffusion (SRID) assay requires a reference antigen and an antibody to the hemagglutinin (HA) of an influenza vaccine. As it takes 2‑3 months to develop the reference antigen, vaccine development is delayed in cases of an influenza pandemic. In the present study, the measurement of the HA content of influenza vaccines was assessed using size exclusion high performance liquid chromatography (SE‑HPLC) for the rapid development of a pandemic vaccine. When the 2009 H1N1 reference antigen, pandemic 2009 H1N1 vaccine and 2010 seasonal influenza vaccines were analyzed by SE‑HPLC, the HA of the reference antigen and vaccines was specifically separated. The presence and specificity of HA were evidenced with immunoprecipitation and ELISA assays. For the influenza vaccines, the chromatogram pattern and retention time of HA were similar among the antigen types (2009 H1N1, 2010 H3N2 and 2010 B). In addition, when SE‑HPLC was applied, the ratio of HA chromatogram to peak area revealed a significant correlation with HA concentration for the reference antigen and vaccine. The result of the HA content calculation based on SE‑HPLC exhibited 99.91‑100% similarity, compared with that of SRID. These findings suggest that the measurement of peak area ratio/HA content using SE‑HPLC may be a substitute for SRID and rapidly measure HA content to enable faster development of a vaccine during an influenza pandemic.

Prostate cancer (PCa) is a global health concern in human males. Recently, it has been known that endocrine-disrupting chemicals (EDCs) may act as an exogenous factor to enhance cancer progression. Triclosan (TCS) and 2,4-dihydroxybenzophenone (BP-1) were reported to bioaccumulate in human bodies through the skin absorption. However, there has been insufficient evidence on the findings that the intervention of EDCs may promote the cancer progression in PCa. In the present study, to verify the risk of TCS and BP-1 to a PCa progression, cancer cell proliferation and migration were investigated in LNCaP PCa cells. TCS and BP-1 increased LNCaP cell proliferative activity and migration as did dihydrotestosterone (DHT). This phenomenon was reversed by the treatment with bicalutamide, a well known AR antagonist, suggesting that TCS and BP-1 acted as a xenoandrogen in LNCaP cells via AR signaling pathway by mimicking the action of DHT. A Western blot assay was performed to identify the alterations in the translational levels of cell growth- and metastasis-related markers, i.e., c-fos, cyclin E, p21, and cathepsin D genes. The expressions of genes related with G1/S transition of cell cycle and metastasis were increased by DHT, TCS, and BP-1, while the expression of p21 protein responsible for cell cycle arrest was reduced by DHT, TCS, and BP-1. Taken together, these results indicated that TCS and BP-1 may enhance the progression of PCa by regulating cell cycle and metastasis-related genes via AR signaling pathway., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Palm oil is a common cooking ingredient used in the commercial food industry as the second largest consumed vegetable oil in the world. Because of its lower cost and highly saturated nature, it usually maintains a solid form at room temperature and is used as a cheap substitute for butter. However, there has been a growing health concern about palm oil because of the link between dietary fats and coronary heart disease. Palm oil contains ∼49% saturated fat, a relatively high concentration compared with other vegetable oils. Consequently, high intakes of saturated fat from palm oil induce a larger increase in plasma concentrations of total cholesterol and low-density lipoproteins. In the present study, we examined the hyperlipidemia of palm oil and the risk of cardiovascular disease (CVD) using a rat model in comparison with sunflower oil with a relatively low level of saturated fat. On in vivo examination using Sprague-Dawley (SD) rats for 22 days, there were no significant differences in serum lipid levels, suggesting that palm oil may not cause hyperlipidemia and elevate CVD risk. However, liver samples obtained from SD rats fed with palm oil showed a lot of large lipid inclusions stained with the Oil Red O working solution, but not much lipid accumulation was observed in rats treated with sunflower oil. In addition, lipid accumulation in the mixed oil group fed the combination of palm and sunflower (1:1) oil was shown to be at an intermediary level between the palm oil group and sunflower oil group. Taken together, these results indicate that palm oil, a highly saturated form of vegetable oil, may induce dysfunction of the liver lipid metabolism before affecting serum lipid levels. On the other hand, sunflower oil, a highly unsaturated vegetable oil, was shown to be well metabolized in liver.

Endocrine-disrupting chemicals (EDC) are defined as environmental compounds that produce adverse health manifestations in mammals by disrupting the endocrine system. Benzophenone-1 (2,4-dihydroxybenzophenone, BP1) and nonylphenol (NP), which are discharged from numerous industrial products, are known EDC. The aim of this study was to examine the effects of BP1 and NP on proliferation and metastasis of MCF-7 human breast cancer cells expressing estrogen receptors (ER). Treatment with BP1 (10⁻⁵-10⁻⁷ M) and NP (10⁻⁶-10⁻⁷ M) promoted proliferation of MCF-7 cells similar to the positive control 17 -beta-estradiol (E2). When ICI 182,780, an ER antagonist, was co-incubated with E2, BP1, or NP, proliferation of MCF-7 cells returned to the level of a control. Addition of BP1 or NP markedly induced migration of MCF-7 cells similar to E2. To elucidate the underlying molecular mechanisms produced by these EDC, alterations in transcriptional and translational levels of proliferation and metastasis-related markers, including cyclin D1, p21, and cathepsin D, were determined. Data showed increase in expression of cyclin D1 and cathepsin D and decrease in p21 at both transcriptional and translational levels. However, BP1- or NP-induced alterations of these genes were blocked by ICI 182,780, suggesting that changes in expression of these genes may be regulated by an ERα-dependent pathway. In conclusion, BP1 and NP may accelerate growth of MCF-7 breast cancer cells by regulating cell cycle-related genes and promote cancer metastasis through amplification of cathepsin D.

Genistein is one of isoflavones mostly derived in a leguminous plant. It is well known as one of phytoestrogens that have structures similar to the principal mammalian estrogen. It has diverse biological functions including chemopreventive properties against cancers. Anticancer efficacies of genistein have been related with the epidemiological observations indicating that the incidence of some cancers is much lower in Asia, where diets are rich in soyfoods, than Western countries. This review deals with in vivo anticancer activities of genistein identified in animal studies being divided into its effects on carcinogenesis and cancer progression. Because animal studies have advantages in designing the experiments to suit the goals, they imply diverse information on the anticancer activity of genistein. The in vivo animal studies have adopted the specific animal models according to a developmental stage of cancer to prove the anticancer efficacies of genistein against diverse types of cancer. The numerous previous studies insist that genistein effectively inhibits carcinogenesis in the DMBA-induced animal cancer models by reducing the incidence of adenocarcinoma and cancer progression in the transgenic and xenograft animal models by suppressing the tumor growth and metastatic transition. Although the protective effect of genistein against cancer has been controversial, genistein may be a candidate for chemoprevention of carcinogenesis and cancer progression and may deserve to be the central compound supporting the epidemiological evidence.

In reviewing the literature, we found few cases of Salmonella osteomyelitis of the femoral diaphysis in a healthy patient. Most are typically associated with sickle cell anemia or immunosuppressed patients. We report on the successful treatment of Salmonella osteomyelitis in the mid-diaphyseal region of the femur caused by Salmonella species in a healthy individual.

According to WHO global estimates from 2008, more than 1.4 billion adults were overweight and among them, over 200 million men and 300 million women were obese. Although the main treatment modalities for overweight and obese individuals remain dieting and physical exercise, the synthetic anti-obesity medications have been increasingly used due to their perceived convenience. Generally, anti-obesity medications are classified as appetite suppressants or fat absorption blockers. In the present study, we examined the adverse side-effects in respect of behavior changes of phentermine and Ephedra sinica (mahuang) that are anti-obesity drugs currently distributed to domestic consumers. Phentermine is mainly classified as an anorexing agent and mahuang a thermogenic agent. Because phentermine and mahuang are considered to display effectiveness through the regulation of nerve system, their potential influences of on behavioral changes were examined employing animal experiments. From the results of experiments testing locomotor activity through the use of treadmill, rota-rod, and open field system, phentermine and mahuang were commonly revealed to induce behavioral changes of rats by reducing a motor ability, an ability to cope with an external stimulus, and a sense of balance or by augmenting wariness or excitement. These adverse effects of phenternime and mahuang in behavioral changes need to be identified in humans and anti-obesity medications such as phentermine and mahuang should be prescribed for only obesity where it is anticipated that the benefits of the treatment outweigh their potential risks.

Phytoestrogens exist in edible compounds commonly found in fruits or plants. For long times, phytoestrogens have been used for therapeutic treatments against human diseases, and they can be promising ingredients for future pharmacological industries. Kaempferol is a yellow compound found in grapes, broccoli and yellow fruits, which is one of flavonoid as phytoestrogens. Kaempferol has been suggested to have an antioxidant and anti-inflammatory effect. In past decades, many studies have been performed to examine anti-toxicological role(s) of kaempferol against human cancers. It has been shown that kaempferol may be involved in the regulations of cell cycle, metastasis, angiogenesis and apoptosis in various cancer cell types. Among them, there have been a few of the studies to examine a relationship between kaempferol and apoptosis. Thus, in this review, we highlight the effect(s) of kaempferol on the regulation of apoptosis in diverse cancer cell models. This could be a forecast in regard to use of kaempferol as promising treatment against human diseases.

The non-animal in vitro test methods, especially for assessment of kidney toxicity, have become invaluable tools due to the target organ-selective nature of many nephrotoxic xenobiotics. In vitro evaluation of biomarkers for nephrotoxicity assessment using human cell lines, which can provide more reliable information for toxicological risk evaluation in humans than animal cells, has not been well established to date. The present study investigated the potential use of biomarkers for cisplatin-induced nephrotoxicity assessment in vitro using HK-2 cells derived from human kidney proximal tubule epithelial cells. Cisplatin induced apoptosis of HK-2 cells in which down-regulation of Bcl-2 and activation of caspase-3 were possibly involved. We investigated the effect of cisplatin on the protein levels of kidney injury molecule (KIM)-1, clusterin, calbindin, tissue inhibitor of metalloproteinase (TIMP)-1, cystatin C (CysC), β₂-microglobulin (β₂-M) and neutrophil gelatinase associated lipocalin (NGAL), which have been recently identified as in vivo biomarkers of nephrotoxicity. The protein levels of KIM-1, calbindin and TIMP-1 were significantly increased in the conditioned media of HK-2 cells treated with cisplatin, while β₂-M, CysC, NGAL and clusterin were not affected by cisplatin treatment. The mRNA levels of KIM-1, calbindin and TIMP-1 were increased by cisplatin, indicating that cisplatin-induced up-regulation involves transcriptional activation. The levels of KIM-1, calbindin and TIMP-1 were significantly increased in urine of cisplatin-treated rats, providing in vivo validation of the in vitro results. Taken together, our results clearly demonstrate that among the known in vivo nephrotoxic biomarkers, KIM-1, calbindin and TIMP-1 can be effectively used as in vitro biomarkers for cisplatin-induced nephrotoxicity using a HK-2 human kidney cell system., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Sixteen UV filters were simultaneously analyzed using the high-performance liquid chromatographic method. They were drometrizole (USAN Drometrizole), 4-methylbenzylidene camphor (USAN Enzacamene), menthyl anthranilate (USAN Menthyl anthranilate), benzophenone-3 (USAN Oxybenzone), benzophenone-8 (USAN Dioxybenzone), butyl methoxydibenzoylmethane (USAN Avobenzone), ethylhexyl triazone (USAN Octyl triazone), octocrylene (USAN Octocrylene), ethylhexyl dimethyl p-aminobenzoic acid (USAN Padimate O), ethylhexyl methoxycinnamate (USAN Octinoxate), p-aminobenzoic acid (USAN Aminobenzoic acid), 2-phenylbenzimidazole-5-sulfonic acid (USAN Ensulizole), isoamyl p-methoxycinnamate (USAN Amiloxate), and recent UV filters such as diethylhexyl butamidotriazone (USAN Iscotrizinol), methylene bis-benzotriazolyl tetramethylbutylphenol (USAN Bisoctrizole), and terephthalylidene dicamphor sulfonic acid (USAN Ecamsule). Separation of the UV filters was carried out in a C(18) column with a gradient of methanol-phosphate buffer, and the UV detection was at 300, 320, or 360 nm without any interference. The limits of detection were between 0.08 and 1.94 μg/ml, and the limits of quantitation were between 0.24 and 5.89 μg/ml. The extracting solvent for the UV filters was methanol, except for ethylhexyl triazone and methylene bis-benzotriazolyl tetramethylbutylphenol, which were prepared with tetrahydrofuran. The recoveries from spiked samples were between 94.90% and 116.54%, depending on the matrixes used. The developed method was applied to 23 sunscreens obtained from local markets, and the results were acceptable to their own criteria and to maximum authorized concentrations. Consequently, these results would provide a simple extracting method and a simultaneous determination for various UV filters, which can improve the quality control process as well as the environmental monitoring of sunscreens.

Leukaraiosis and a higher level of pulse pressure are well-recognized as associated with cardiovascular disease, vascular angiopathy, and geriatric syndrome. A cross-sectional study was conducted to examine the relation between pulse pressure and leukoaraiosis based on brain magnetic resonance imaging (MRI) scans in the apparently healthy elderly (147 men aged 60-84 years and 89 women aged 60-82 years). The odds ratios (OR) and 95% confidence interval (CI) for leukoaraiosis were calculated using multivariate logistic regression analyses according to each quartile of pulse pressure. The percentage of leukoaraiosis gradually increased in accordance with pulse pressure quartiles: 5.1%, 8.6%, 16.1%, and 26.2% for men, and 4.5%, 8.7%, 13.0%, and 23.8% for women. In comparison with subjects in the lowest quartile, the OR (95%CI) for leukoaraiosis in the highest quartile was 6.80 (1.20-38.45) in men after adjusting for age, body mass index, fasting plasma glucose, HDL-cholesterol, triglyceride (TG), smoking status, and current drinking. However, the relationship was not evident in women after adjusting for the same co-variables. In conclusion, pulse pressure was found to be independently associated with leukoaraiosis regardless of classical cardiovascular risk factors in elderly men., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

A growing list of membrane-spanning proteins involved in the transport of a large variety of drugs has been recognized and characterized to include peptide and organic anion/cation transporters. Given such an important role of transporter genes in drug disposition process, the role of single-nucleotide polymorphisms (SNPs) in such transporters as potential determinants of interindividual variability in drug disposition and pharmacological response has been investigated. To define the distribution of transporter gene SNPs across ethnic groups, we screened 450 DNAs in cohorts of 250 Korean, 50 Han Chinese, 50 Japanese, 50 African-American and 50 European-American ancestries for 64 SNPs in four transporter genes encoding proteins of the solute carrier family (SLC15A2, SLC22A1, SLC22A2 and SLC22A6). Of the 64 SNPs, 19 were core pharmacogenetic variants and 45 were HapMap tagging SNPs. Polymorphisms were genotyped using the golden gate genotyping assay. After genetic variability, haplotype structures and ethnic diversity were analyzed, we observed that the distributions of SNPs in a Korean population were similar to other Asian groups (Chinese and Japanese), and significantly different from African-American and European-American cohorts. Findings from this study would be valuable for further researches, including pharmacogenetic studies for drug responses.

Embryonic stem cell (ESC) research gave rise to the possibility that stem cell therapy could be used in the treatment of incurable diseases such as neurodegenerative disorders. However, problems related to the tumorigenicity of undifferentiated ESCs must be resolved before such cells can be used in the application of cell replacement therapies. In the present study, we attempted to determine biomarkers that predicted tumor formation of undifferentiated ESCs in vivo. We differentiated mouse ESCs (R1 cell line) into neural lineage using a 5-step method, and evaluated the expression of oncogenes (p53, Bax, c-myc, Bcl2, K-ras), telomerase-related genes (TERT, TRF), and telomerase activity and telomere length during differentiation of ESCs. The expression of oncogenes did not show a significant change during differentiation steps, but the expression of telomerase reverse transcriptase (TERT) and telomerase activity correlated with mouse ESCs differentiation. To investigate the possibility of mouse TERT (mTERT) as a biomarker of tumorigenicity of undifferentiated ESCs, we established mTERT knockdown ESCs using the shRNA lentivirus vector and evaluated its tumorigenicity in vivo using nude mice. Tumor volumes significantly decreased, and appearances of tumor formation in mice were delayed in the TERT-knockdown ESC treated group compared with the undifferentiated ESC treated group. Altogether, these results suggested that mTERT might be potentially beneficial as a biomarker, rather than oncogenes of somatic cells, for the assessment of ESCs tumorigenicity.

Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last)). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach.

Our goal in the present study was to evaluate whether decabromodiphenyl ether (BDE-209), which is the most abundant polybrominated diphenyl ether (PBDE) found in human samples, affects against target organs. Sprague-Dawley male rats were exposed to vehicle or BDE-209 (100, 300, or 600 mg/kg body weight, daily) from postnatal day (PND) 10 to PND 42. There was no significant difference in body and male reproductive organ weight changes compared with controls. However, liver, thyroid and adrenal gland weights were significantly increased in the high-dose of BDE-209 group. BDE-209 significantly induced the expression of cytochrome P450 (CYP1A2, CYP3A1, and CYP2B1) enzymes in the liver. Furthermore, constitutive androstane receptor (CAR) and pregnane xenobiotic receptor (PXR) expression levels were also increased in a dose-dependent manner. Total serum triiodothyronine (T3) concentration was significantly reduced in a dose-dependent manner, whereas the level of thyroid-stimulating hormone was significantly increased with BDE-209 treatment. In the histological findings, multiple areas of degenerated follicular epithelium and slight attenuation of the follicular epithelium were observed in the thyroid glands by high doses (300 and 600 mg/kg) of BDE-209 treatment. The presence of hepatocytic fatty degeneration and inflammatory foci were also observed in the 300 and 600 mg/kg of BDE-209 group. These findings demonstrate that BDE-209 induces hyperthyroidism and hepatotoxicity. In the future, further research is needed to determine the relationship between target organ toxicity and blood concentrations of BDE-209.