Anti-photoaging effects of canola meal extract on human dermal fibroblasts against UVB-induced oxidative stress.

Canola meal, a by-product of canola oil processing, is a source of bioactive compounds that show antioxidant and skin anti-aging effects through upcycling (i.e., creative reuse). Here we describe the antioxidant and skin anti-aging effects of canola meal extract (CME) obtained by upcycling canola meal. The antioxidant capacity of CME is due in part to its antioxidative phenolics. Seven phenolics, including sinapine and sinapic acid, in CME were identified using ultra-high-performance liquid chromatography-Orbitrap mass spectrometry. Addition of CME (1000 µg/mL) to human dermal fibroblast neonatal cells  significantly (p < 0.05) reduced matrix metalloproteinase-12 production and increased pro-collagen Ι alpha 1 content in response to ultraviolet B-induced oxidative stress compared with cells without CME. These results suggest that CME can serve as a functional food ingredient with antioxidant capacity and anti-aging effects on the skin.

The Association of Perfluoroalkyl Substance Exposure and a Serum Liver Function Marker in Korean Adults.

Perfluoroalkyl substances (PFAS), widely used throughout industry and daily life, are currently one of the environmental pollutants garnering the most attention worldwide. Recently, environmental pollutants have had a high profile as one of the main causes of chronic liver disease, such as non-alcoholic fatty liver disease. Research on PFAS is actively underway. Although Korea has a remarkably high prevalence of chronic liver disease, and it continues to increase, only a few studies have revealed the relationship between PFAS and liver disease. In addition, regulations on PFAS in Korea are delayed compared to developed countries, such as Europe and the United States, and public interest is insufficient compared to others. Therefore, we would like to investigate the exposure of Koreans to PFAS in the blood and examine the relationship between these substances and markers of liver function (AST, ALT, and GGT). This study was based on the results of the Korean National Environmental Health Survey (KoNEHS) 2018­2020 (Cycle 4), and a total of 2961 subjects were selected. The concentration of PFAS in the blood of Korean adults was measured to be significantly higher based on the geometric mean compared to the results of recently investigated American adults based on the National Health and Nutrition Examination Survey (NHANES, 2017-2018). A multivariable linear regression analysis adjusted for age, sex, body mass index (BMI), smoking status, alcohol intake, and regular exercise was performed to examine changes in three liver function markers as the serum PFAS concentration increased. We found that some of the five PFAS (PFOA, PFOS, PFHxS, PFNA, and PFDeA) were significantly associated with increased liver enzymes. It is necessary to recognize the threat of PFAS to the human body and to discuss regulations and alternatives in earnest. Continuous follow-up studies are required through a well-designed cohort.

Relationship between job stress and impaired fasting glucose in male steel industry workers: a cross-sectional study.

Background: The purpose of this study is to investigate the relationship between job stress and impaired fasting glycemia (IFG) of male workers in a manufacturing industry. Methods: Data were collected from 5,886 male workers in a manufacturing industry who participated in the medical examination from June 19 to August 14, 2020 through self-reported questionnaires. The general characteristics of the subjects, shift work, high blood pressure, dyslipidemia, and job stress were included. Job stress was measured using the Korean Occupational Stress Scale (KOSS) consisting of 8 items and 43 questions. Multivariable logistic regression analysis was used to investigate the IFG association with job stress. Results: Among the various factors that can cause job stress, only high job demand was associated with a risk of IFG (odds ratio, 1.43; 95% confidence interval, 1.13-1.82) especially in non-shift worker. For all other factors, no statistically significant results were obtained. Conclusions: In this study of male workers engaged in the Korean steel manufacturing industry, the 'job demand' item among job stress of non-shift worker was related to IFG.

The association of perfluoroalkyl substances (PFAS) exposure and kidney function in Korean adolescents using data from Korean National Environmental Health Survey (KoNEHS) cycle 4 (2018-2020): a cross-sectional study.

Background: Perfluoroalkyl substances (PFAS) are chemicals widely used in various products in everyday life. Due to its unique strong binding force, the half-life of PFAS is very long, so bioaccumulation and toxicity to the human body are long-standing concerns. In particular, effects on kidney function have recently emerged and there are no studies on the effect of PFAS on kidney function through epidemiological investigations in Korea. From 2018 to 2020, the Korean National Environmental Health Survey (KoNEHS) cycle 4, conducted an epidemiological investigation on the blood concentration of PFAS for the first time in Korea. Based on this data, the relationship between PFAS blood concentration and kidney function was analyzed for adolescents. Methods: We investigated 5 types of PFAS and their total blood concentration in 811 middle and high school students, living in Korea and included in KoNEHS cycle 4, and tried to find changes in kidney function in relation to PFAS concentration. After dividing the concentration of each of the 5 PFAS and the total concentration into quartiles, multivariable linear regression was performed to assess the correlation with kidney function. The bedside Schwartz equation was used as an indicator of kidney function. Results: As a result of multivariable linear regression, when observing a change in kidney function according to the increase in the concentration of each of the 5 PFAS and their total, a significant decrease in kidney function was confirmed in some or all quartiles. Conclusions: In this cross-sectional study of Korean adolescents based on KoNEHS data, a negative correlation between serum PFAS concentration and kidney function was found. A well-designed longitudinal study and continuous follow-up are necessary.

The acclimatization of Haenyeo to a cold environment and occupational characteristics evaluated by orexin and irisin levels.

Background: Haenyeo is a woman who has the job of collecting seafood in the Jeju Sea at an average temperature of 13°C-14°C. The purpose of this study was to examine the cold acclimatization and occupational characteristics of Haenyeo through biomarkers such as orexin and irisin related to heat generation in the body. Methods: Twenty-one Haenyeo and 25 people with similar age, body type, and body mass index were selected as the control group (Control G). In the cold exposure experiment, a climate chamber was set to 5°C and both feet were immersed in a 15°C water tank for 30 minutes. Tympanic temperature (Tty) and skin temperature (Tsk) were measured, and the mean body temperature (mTb) was calculated. Blood samples were collected before and immediately after the examination. Orexin and irisin levels were analyzed. Results: Orexin levels were elevated after cold stimulation from 12.17 ± 4.44 to 12.95 ± 4.53 ng/mL (Haenyeo group [Haenyeo G], p < 0.01) and 10.37 ± 3.84 to 11.25 ± 4.02 ng/mL (Control G, p < 0.001). Irisin levels were elevated after cold stimulation from 4.83 ± 2.28 to 5.36 ± 2.23 ng/mL (Haenyeo G, p < 0.001) and 3.73 ± 1.59 to 4.18 ± 2.04 ng/mL (Control G, p < 0.001). The difference between Haenyeo G and Control G values in orexin and irisin appears not only in pre-exposure but also in post-exposure (p < 0.05). Conclusions: Our experimental results suggest that Haenyeo G were relatively superior in cold tolerance to Control G under cold exposure conditions. Haenyeo's cold acclimatization is due to the basic differences in pyrogens regarding body temperature control such as orexin and irisin. This means that Haenyeo are advantageous for cold survival.

Isolation and structural characterization of a novel sibutramine analogue, chlorosipentramine, in a slimming dietary supplement, by using HPLC-PDA, LC-Q-TOF/MS, FT-IR, and NMR.

A novel sibutramine analogue was detected in a slimming formula by high performance liquid chromatography with a photo diode detector array (HPLC-PDA). The unknown compound exhibited an ultraviolet (UV) spectrum that was similar to that of chlorosibutramine, despite having a different HPLC retention time. Further analysis of the slimming formula by LC-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) showed that the unknown compound had the formula C18H27Cl2N. To elucidate the structure of this new sibutramine analogue, the target compound in the slimming formula was isolated on a preparative-LC system equipped with a PDA. After analysis by fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy, the unknown compound was identified as a sibutramine analogue in which the iso-butyl group on the side chain is replaced with an iso-pentyl group. This new sibutramine analogue was identified to be 1-(1-(3,4-dichlorophenyl)cyclobutyl)-N,N,4-trimethylpentan-1-amine and has been named as chlorosipentramine.

Identification and structural elucidation of a new sildenafil analogue, dithiopropylcarbodenafil, from a premixed powder intended as a dietary supplement.

A new sildenafil analogue was detected during the monitoring of a premixed powder intended as a dietary supplement. The ultraviolet (UV) spectrum of the unknown compound was similar to that of dithiodesmethylcarbodenafil and dithiodesethylcarbodenafil, although their corresponding HPLC peaks were observed at different retention times. The chemical structure of the unknown compound was characterized by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS), followed by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy. The comparison of its structure with that of dithiodesmethylcarbodenafil, revealed that the N-methyl group on the piperazine ring is replaced by a propyl group. This new sildenafil analogue was identified as 5-(2-ethoxy-5-(4-propylpiperazine-1-carbonothioyl)phenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidine-7-thione and designated as a dithiopropylcarbodenafil. To the best of our knowledge, this is the first study reporting the identification and characterization of dithiopropylcarbodenafil.

Monitoring of the amphetamine-like substances in dietary supplements by LC-PDA and LC-MS/MS.

Recently, amphetamine-like substances derived from the ß-phenylethylamine core structure have been detected in dietary supplements. Especially, ß-methylphenylethylamine (BMPEA), an amphetamine isomer, has been found in dietary supplements labeled as containing Acacia rigidula. The U. S. Food and Drug Administration determined that BMPEA is not naturally present in food and does not meet the statutory definition of a dietary ingredient. In addition, BMPEA has been classified as a psychotropic drug in South Korea and a doping substance by the World Anti-Doping Agency. The aim of this study was to determine whether dietary supplements contained amphetamine and amphetamine-like substance, including ß-phenylethylamine (ß-PEA) and BMPEA using LC-PDA and LC-MS/MS. In 10 of 110 samples, illegally added compounds were detected in the following ranges; ß-PEA 1.4-122.0 mg/g and BMPEA 4.7-37.6 mg/g. This study will contribute to enhancement of food safety in the South Korea.

End-Site-Specific Conjugation of Enoxaparin and Tetradeoxycholic Acid Using Nonenzymatic Glycosylation for Oral Delivery.

Heparin and low molecular weight heparins (LMWHs) have been the drug of choice for the treatment or the prevention of thromboembolic disease. Different methods are employed to prepare the LMWHs that are clinically approved for the market currently. In particular, enoxaparin, which has a reducing sugar moiety at the end-site of polysaccharide, is prepared by alkaline depolymerization. Focusing on this end-site-specific activity of LMWHs, we conjugated the tetraoligomer of deoxycholic acid (TetraDOCA; TD) at the end-site of enoxaparin via nonenzymatic glycosylation reaction. The end-site-specific conjugation is important for polysaccharide drug development because of the heterogeneity of polysaccharides. This study also showed that orally active enoxaparin and tetraDOCA conjugate (EnoxaTD) had therapeutic effect on deep vein thrombosis (DVT) without bleeding in animal models. Considering the importance of end-specific conjugation, these results suggest that EnoxaTD could be a drug candidate for oral heparin development.

A polymorphism in the YWHAH gene encoding 14-3-3 eta that is not associated with sporadic Creutzfeldt-Jakob disease (CJD).

14-3-3 proteins are abundantly expressed in the brain, particularly neuronal tissue and are thought to serve multiple biological functions involved in neuronal development and cell growth and death. Recent studies have shown associations of 14-3-3 genes with neurodegenerative disorders based on their chromosomal linkage to these diseases and to regulatory functions for the nervous system. Although the role of 14-3-3 proteins in the pathogenesis of prion diseases remains unknown, the detection of altered levels of isoforms of the 14-3-3 protein in the cerebrospinal fluid is considered a biomarker for diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). To identify other susceptibility genes for prion disease, we examined nucleotide variations in YWHAH, a gene encoding 14-3-3 eta. This case-control study included 182 sCJD patients and 206 healthy Koreans. Polymerase chain reaction was used to amplify open reading frame and some 3'-untranslated region (UTR) in exon 2, and direct sequencing was carried out. One polymorphism, 753 G/A, was detected in the 3'-UTR of exon 2 on the YWHAH. The genotype distribution and allele frequencies of the YWHAH 753 G/A polymorphism were not significantly different between controls and sCJD patients. This finding indicates that YWHAH 753 G/A polymorphism is unlikely to be linked to genetic susceptibility or have a modifying effect in sCJD. On analysis stratified by the prion protein gene 129 or 219 genotype, no significant relation was found in genotype and allele frequencies of the YWHAH 753G/A. This is the first genetic association study of YWHAH with sCJD populations.

The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD).

BACKGROUND: Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s) modulating susceptibility to prion disease. Ribosomal protein SA (RPSA), also called 37 kDa laminin receptor precursor (LRP)/67 kDa laminin receptor (LR), acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR. METHODS: To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD) patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP) analysis. RESULTS: We observed four single nucleotide polymorphisms (SNPs), including -8T>C (rs1803893) in the 5'-untranslated region (UTR) of exon 2, 134-32C>T (rs3772138) in the intron, 519G>A (rs2269350) in the intron and 793+58C>T (rs2723) in the intron on the RPSA. The 519G>A (at codon 173) is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. CONCLUSION: These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.

Absence of association between two HECTD2 polymorphisms and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: HECT (homologous to E6-AP carboxyl terminus) E3 ubiquitin ligases are fundamental components of the eukaryotic ubiquitin-proteasome system and are involved in the pathogenesis of several human diseases, including polyglutamine diseases. HECTD2, an E3 ubiquitin ligase, has been linked to the incubation time of prion disease in mice, and its polymorphisms have been associated with sporadic Creutzfeldt-Jakob disease (CJD) in the British population. OBJECTIVE: To investigate whether 2 HECTD2 polymorphisms, -247G→A (rs7081363) and +16066T→A (rs12249854), are associated with sporadic CJD in the Korean population. METHODS: We compared the genotype, allele and haplotype frequencies of the 2 HECTD2 polymorphisms in 205 sporadic CJD patients to those of 208 healthy Koreans. RESULTS AND CONCLUSION: Our study does not show significant differences in the genotype and allele frequencies of these 2 polymorphisms between sporadic CJD and normal controls. Significant differences in the haplotype frequencies of these 2 polymorphisms were not observed between sporadic CJD and normal controls either. Our results indicate that these 2 HECTD2 polymorphisms are not associated with genetic susceptibility to sporadic CJD in a Korean population. This is the first genetic association study of HECTD2 with sporadic CJD in an Asian population.

Associations of plasma homocysteine level with brachial-ankle pulse wave velocity, LDL atherogenicity, and inflammation profile in healthy men.

AIMS: To investigate the association of plasma total homocysteine (tHcy) with arterial stiffness, measured as brachial-ankle pulse wave velocity (baPWV), LDL atherogenicity, and inflammation profile in healthy men. METHODS AND RESULTS: In this cross-sectional study, 612 healthy men aged 31-79 years were classified into quartiles according to plasma tHcy concentration. In the total study population, tHcy concentration showed positive correlation with age (r=0.083, P=0.040), interleukin (IL)-1ß (r=0.249, P<0.001), TNF-α (r=0.150, P<0.001), IL-6 (r=0.154, P<0.001), oxidized LDL (oxLDL) (r=0.161, P=<0.001), and baPWV (r=0.087, P=0.032); and negative correlation with folate (r=-0.353, P<0.001) and vitamin B(12) (r=-0.269, P<0.001). In subgroup analysis based on plasma tHcy level, tHcy was associated with baPWV in men with high levels of tHcy (≥ 13.1µmol/L, n=153; r=0.258, P=0.001), but not in those with low-tHcy (<13.1 µmol/L, n=459; r=-0.033, P=0.478). The association between tHcy and baPWV in the high-tHcy group remained significant after adjustment for age, BMI, smoking, drinking, folate, and vitamin B12. In the high-tHcy group, tHcy level was also positively correlated with IL-1ß, TNF-α, oxLDL, and blood pressure; and negatively correlated with LDL particle size. In addition, baPWV showed negative correlation with LDL particle size and positive correlation with oxLDL in the high-tHcy group. CONCLUSION: This study shows an association between high levels of plasma tHcy and more advanced arterial stiffness, smaller LDL particle size, and higher levels of oxLDL and cytokines in men with hyperhomocysteinemia. Enhanced arterial stiffness in hyperhomocysteinemia might be attributed, in part, to Hcy-related LDL atherogenicity.

Genetic association of a cathepsin D polymorphism and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Cathepsin D is the most abundant lysosomal and endosomal aspartyl protease; it shows beta and gamma secretase activity in vitro by cleaving the amyloid precursor protein into amyloid beta protein. In recent studies, cathepsin D was co-localized with PrP(Sc), the disease-associated form of the prion disease, and abnormal expression of cathepsin D correlated with tissue damage in brains of sporadic Creutzfeldt-Jakob disease (CJD). OBJECTIVE: To investigate whether a polymorphism at position 224, C224T, on exon 2 of the cathepsin D gene (CTSD) is associated with sporadic CJD in the Korean population. METHODS: We compared the genotype and allele frequencies at this polymorphism site in 172 sporadic CJD patients with those in 197 healthy Koreans. RESULTS AND CONCLUSION: Our study does not show a significant difference in genotype (p = 0.901) and allele (p = 0.509) frequencies of CTSD C224T between sporadic CJD patients and normal controls. This was the first genetic association study of CTSD in a sporadic CJD population.