Curcumol metabolized by rat liver S9 fraction and orally administered in mouse suppressed the proliferation of colon cancer in vitro and in vivo.

Following 3R (reduction, refinement, and replacement) principles, we employed the rat liver S9 fraction to mimic liver metabolism of curcumol having high in vitro IC50 on cancer cells. In HCT116 and HT29 colon cancer cells, the metabolites of curcumol by S9 fraction exerted more enhanced activity in inducing cell cycle arrest and apoptosis via regulating the expression of cyclin D1, CDK1, p21, PARP and Bcl-2 than curcumol. In addition, oral administration of curcumol at 4 mg/kg BW significantly suppressed the development of colon tumor induced by azoxymethane/dextran sulfate sodium, and induced cell cycle arrest and apoptosis in tumor tissues. In mass analysis, curcumenol and curzerene were identified as the metabolites of curcumol by S9 fraction metabolism. Taken together, curcumol metabolites showed the enhanced suppressive effect on colon cancer, suggesting that S9 fraction can be considered as simple, fast, and bio-mimicking platform for the screening of chemical libraries on different chronic diseases.

Clinical features at the time of non-hysteroscopic myomectomy before pregnancy, which affect adverse pregnancy outcomes: a retrospective cohort study.

BACKGROUND: To investigate the association of clinical characteristics at the time of non-hysteroscopic myomectomy before pregnancy and adverse obstetric outcomes in the next pregnancy. METHODS: In this retrospective cohort study, we identified 248 women who underwent abdominal or laparoscopic myomectomy for intramural (IM) and/or subserosal (SS) uterine myomas in Bundang CHA Medical Center before pregnancy and delivered at the same hospital between 2010 and 2020. The association between clinical characteristics at the time of myomectomy and subsequent obstetric outcomes was analyzed using the Chi-square test, the Student t-test or one-way ANOVA, and multivariable analysis. RESULTS: There was one case of uterine rupture. The gestational age at delivery was 37.7 ± 2.4 weeks. There were 2 (0.8%) cases of fetal loss before 23 weeks, but there were no cases of perinatal death. The risk of transfusion during or after delivery was higher in the group in which multiple myomas were removed compared to the group in which only one was removed (aOR = 2.41, 95% CI [1.20-4.86], p = 0.014). The risk of neonatal composite morbidity was higher in the group in which myomas including the IM type were removed, than in the group in which only SS myomas were removed (aOR = 14.29, 95% CI [1.82-99.57], p = 0.012). Although not statistically significant, the group in which the sum of the diameters of the three largest myomas was greater than 15 cm showed a higher frequency of preterm birth (19.3% vs. 10.1%, p = 0.001) and lower birth weight (2901 ± 625 g vs. 3063 ± 576 g, p = 0.001) compared to the group with diameters less than 15 cm. Placenta accreta/increta (7.9% vs. 3.8%, p = 0.043) and lower placental weight (646 ± 170 g vs. 750 ± 232 g, p = 0.034) were more common in patients with an interval between myomectomy and pregnancy of less than 12 months compared to more than 12 months. CONCLUSIONS: To our knowledge, this is the first study to investigate the association between clinical features at the time of myomectomy before pregnancy and various adverse obstetric and perinatal outcomes. If the removed myomas are multiple, IM, large, or the interval between myomectomy and pregnancy is short, the risk of obstetric and neonatal complications may increase.

Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model.

Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.

Water Extract of Mixed Mushroom Mycelia Grown on a Solid Barley Medium Is Protective against Experimental Focal Cerebral Ischemia.

Although the individual consumption of medicinal mushrooms, including Phellinus linteus (PL), Ganoderma lucidum (GL), and Inonotus obliquus (IO), is known to be neuroprotective, the associated mechanisms underlying their therapeutic synergism on focal cerebral ischemia (fCI) have yet to be elucidated. This study aimed to demonstrate the neuroprotective effects of mixed mushroom mycelia (MMM) against experimental fCI. The water-fractions, ethanolic-fractions, and ethyl acetate-fractions of the MMM (PL, GL, and IO) grown in a barley medium using solid-state fermentation techniques were prepared and their protective effects against glutamate-induced excitotoxicity were compared in PC-12 cells. After the identification of the water extracts of MMM (wMMM) as the most suitable form, which possessed the lowest toxicity and highest efficacy, further analyses for evaluating the anti-apoptotic effects of wMMM, including Hoechst 33258-based nuclear staining, fluorescence-activated cell sorting, and reactive oxygen species (ROS) detection assays, were performed. Rats were subjected to a 90 min middle cerebral artery occlusion and reperfusion, after which a wMMM treatment resulted in significant dose-dependent improvements across a number of parameters. Furthermore, measurements of intracellular ROS and levels of antioxidant enzymes revealed a wMMM-mediated ROS attenuation and antioxidant enzyme upregulation. We suggest that wMMM is neuroprotective against fCI through its anti-apoptotic and anti-oxidative effects.

Freeze-Dried Powder of Rubus coreanus Miquel Ameliorates Isoproterenol-Induced Oxidative Stress and Tissue Damage in Rats.

Rubus coreanus Miquel (bokbunja), Korean black raspberry, is known to possess various phytochemicals that exert antioxidative, anti-inflammatory, and anti-cancer effects. However, most studies on Rubus coreanus Miquel have been performed with the solvent extracts and/or a single component to demonstrate the efficacy, while studies evaluating the effect of the whole fructus of Rubus coreanus Miquel are limited. In this study, therefore, we employed the isoproterenol (IPN)-induced myocardial infarction model and investigated the effect of freeze-dried powder of Rubus coreanus Miquel (RCP) on oxidative stress and prevention of organ damage. Oral administration of RCP reduced the level of toxicity markers, alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) without affecting body weight and diet intake. The oxidative stress marker glutathione (GSH) increased about 45% and malonaldehyde (MDA) decreased about 27% compared to the IPN group with RCP-H (3%) administration. By histological analysis, IPN induced significant myocardial damage in the heart and vascular injury in the liver, and RCP administration ameliorated the damages in a dose-dependent manner. Taken together, RCP activated the antioxidant system leading to prevention of damage to organs by IPN in rats, making it possible to expect beneficial efficacies by consuming the whole fructus of Rubus coreanus Miquel.

Sedentary Lifestyle: Overview of Updated Evidence of Potential Health Risks.

One-third of the global population aged 15 years and older engages in insufficient physical activities, which affects health. However, the health risks posed by sedentary behaviors are not well known. The mean daily duration of sedentary behavior is 8.3 hours among the Korean population and 7.7 hours among the American adult population. Sedentary lifestyles are spreading worldwide because of a lack of available spaces for exercise, increased occupational sedentary behaviors such as office work, and the increased penetration of television and video devices. Consequently, the associated health problems are on the rise. A sedentary lifestyle affects the human body through various mechanisms. Sedentary behaviors reduce lipoprotein lipase activity, muscle glucose, protein transporter activities, impair lipid metabolism, and diminish carbohydrate metabolism. Furthermore, it decreases cardiac output and systemic blood flow while activating the sympathetic nervous system, ultimately reducing insulin sensitivity and vascular function. It also alters the insulin-like growth factor axis and the circulation levels of sex hormones, which elevates the incidence of hormone-related cancers. Increased sedentary time impairs the gravitostat, the body's weight homeostat, and weight gain, adiposity, and elevated chronic inflammation caused by sedentary behavior are risk factors for cancer. Sedentary behaviors have wide-ranging adverse impacts on the human body including increased all-cause mortality, cardiovascular disease mortality, cancer risk, and risks of metabolic disorders such as diabetes mellitus, hypertension, and dyslipidemia; musculoskeletal disorders such as arthralgia and osteoporosis; depression; and, cognitive impairment. Therefore, reducing sedentary behaviors and increasing physical activity are both important to promote public health.

Garcinone C suppresses colon tumorigenesis through the Gli1-dependent hedgehog signaling pathway.

BACKGROUND: Although garcinone C, a natural xanthone derivative identified in the pericarp of Garcinia mangostana, has been demonstrated to exert different health beneficial activities in oxidative stress and ß-amyloid aggregation, the role of garcinone C in colon tumorigenesis has not been investigated. In addition, aberrant Hedgehog (Hh) signaling activation is associated with tumorigenesis including colon cancer. Here, we hypothesized that garcinone C can prevent colon tumorigenesis through regulating the Hh signaling pathway. METHOD: Colony formation assay and flow cytometry were used to evaluate the effect of garcinone C on the proliferation and cell cycle progression of colon cancer cells. Protein expression of cell cycle related markers and Hh/Gli1 signaling mediators were determined. The regulatory effect of orally administered garcinone C on the Hh/Gli1 signaling pathway and colon tumorigenesis was evaluated in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer animal model. RESULTS: Garcinone C suppressed the proliferation of colon cancer cells, induced G0/G1 cell cycle arrest, as well as regulated the expression of cell cycle-related markers such as cyclin D1, cyclin E, CDK6, and p21. Garcinone C inhibited the expression of Gli1, a key mediator of Hedgehog signaling, and protein kinase B (AKT) phosphorylation in Smo-independent colon cancer cells. In the AOM/DSS-induced colon tumorigenesis model, garcinone C significantly inhibited tumor development, regulated the expression of cell cycle markers and Gli1, and reduced AKT phosphorylation in colon tumor tissues, which is consistent with our in vitro results. CONCLUSION: Garcinone C can suppress colon tumorigenesis in vitro and in vivo through Gli1-dependent non-canonical Hedgehog signaling, suggesting that it may serve as a potent chemopreventive agent against colon tumorigenesis.

Relationship between visual acuity and muscle mass in the Korean older population: a cross-sectional study using Korean National Health and Nutrition Examination Survey.

OBJECTIVES: We aimed to assess the effects of visual acuity on muscle mass, which is an important indicator of health in older populations. DESIGN: Pooled-sample cross-sectional study. SETTING: Nationally representative population survey data. PARTICIPANTS: The present study analysed men aged 65 years or older who participated in the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2011). PRIMARY AND SECONDARY OUTCOME MEASURES: Muscle mass was measured by dual-energy X-ray absorptiometry scan, and low muscle mass was defined as appendicular skeletal mass divided by height squared (kg/m2) <6.43 kg/m2 (lowest quintile of the older population in KNHANES, 2008-2011). Visual acuity was evaluated based on best-corrected visual acuity of the better eye. RESULTS: Of the 1733 participants, 89.9% had good visual acuity. After adjusting for age, the height-adjusted appendicular skeletal muscle mass values were 7.16 and 7.00 kg/m2 in the good and poor vision groups, respectively (p=0.042). According to our criterion for low muscle mass, the prevalence of low muscle mass was 16.4% and 34.7% in the good and poor vision groups, respectively. After adjusting for age, smoking status, alcohol consumption status, frequency of physical activity, educational level, the status of basic livelihood recipient and history of stroke, the poor visual acuity group had higher odds of low muscle mass than the good visual acuity group (OR=1.60; 95% CI 1.02 to 2.50; p=0.040). CONCLUSIONS: Older men with decreased visual acuity have low muscle mass. Poor vision might be an indicator of low muscle mass.

Association between Colorectal Adenoma and Hand Grip Strength in the Elderly.

BACKGROUND: Obesity is known as an important risk factor for colorectal adenoma. However, for the elderly with changes in body composition, reduced muscle, and increased fat, the body mass index (BMI), one of the most commonly used indicators of obesity, is limited in predicting a link to colorectal cancer. This study aimed to investigate the relationship between colorectal adenoma and grip strength that can predict muscle reduction in the elderly. METHODS: This study included 262 participants aged ≥65 years who underwent medical examination between June 2015 and August 2018. The control group comprised participants with normal findings or hyperplasia and other benign lesions, except adenoma on colonoscopy, whereas the adenoma group consisted of participants with more than one adenoma. Grip strength was alternately measured twice for each hand using a hydraulic dynamometer. RESULTS: The grip strength was statistically lower in the adenoma group than in the control group among women (P=0.042). For both sexes, grip strength was significantly lower in participants with ≥5 adenomas than in those with <5 adenomas (P=0.021, P=0.007). Similarly, men with large adenomas (≥7 mm) exhibited significantly lower grip strength than did those with small adenomas (<7 mm) (P=0.004). Even after correction for age, BMI, smoking status, alcohol consumption, exercise, insulin resistance, hypertension, and diabetes, the negative correlation between grip strength and number of adenomas among men and women remained (P=0.034, P=0.019). CONCLUSIONS: A significant relationship between hand grip strength and number of colorectal adenomas was noted.

Low Muscle Mass and Depressed Mood in Korean Adolescents: a Cross-Sectional Analysis of the Fourth and Fifth Korea National Health and Nutrition Examination Surveys.

BACKGROUND: Muscle mass and muscle function are related to depressed mood in studies of adults. Like adults, Korean students are highly likely to suffer from decreased muscle mass due to social conditions. In this study, we evaluated the muscle mass status of Korean adolescents and assess the effect of muscle on depressive mood. METHODS: A total of 1,233 adolescent boys and girls participants from the Korea National Health and Nutrition Examination Survey were enrolled in our study. Participants underwent dual-energy X-ray absorptiometry for assessment of appendicular muscle mass and completed questionnaires regarding depressed mood, stress, suicidal ideations, and attempts. RESULTS: There was no difference in depressive mood according to muscle mass among boys (P = 0.634); girls with decreased muscle mass had a greater tendency for depressed mood compared to girls with optimal muscle mass (P = 0.023). After adjusting for age, waist circumference-to-height ratio, smoking status, alcohol consumption, frequency of physical activity, self-reported obesity, weight-loss efforts, and monthly household income, girls with low muscle mass (LMM) were 2.60 times more at risk of developing depression than girls with normal muscle mass (95% confidence interval [CI], 1.05-6.49; P = 0.040). This trend was similar for girls with LMM with obesity (95% CI, 1.00-11.97; P = 0.049). CONCLUSION: Adolescent girls who have insufficient muscle mass are more likely to report depressed mood than girls who have ideal muscle mass. Interventions for maintaining proper muscle mass are required.

Effect of Secondhand Smoking, Determined by Urinary Cotinine Level on Bone Health.

BACKGROUND: We evaluated the relationship between secondhand smoke (SHS) inhalation, as verified by urinary cotinine levels, and bone health. METHODS: We analyzed the nationwide, population-based, cross-sectional health survey. We included 1936 men aged 50 years or older who checked bone mineral density (BMD) from the Korean National Health and Nutrition Examination Survey (2008-2010). Current smokers assessed by urinary cotinine levels higher than 500 ng/mL were excluded (n = 616). Exposure to SHS was determined using a 50 ng/mL urinary cotinine threshold. RESULTS: The estimated prevalence of SHS exposure in our cohort was 13.9%. After adjusting for age and body mass index (BMI), T-scores at total femur (P < 0.001), femoral neck (P < 0.001), and lumbar spine (P = 0.004) were lower in SHS exposure versus nonexposure groups. Impaired bone health (osteopenia or osteoporosis) at femoral neck or lumbar spine was evident in 61.7% and 48.6% of SHS exposure and nonexposure cases, respectively (P = 0.004). Moreover, after adjusting for age, BMI, and health habits, the odds ratio for impaired bone health in the SHS exposure group was 1.89 (95% confidence interval: 1.31-2.74). CONCLUSIONS: Our findings suggest that SHS exposure, determined by urinary cotinine levels, is negatively associated with BMD and is a leading cause of impaired bone health in Korean men.

Implication of Sarcopenia and Sarcopenic Obesity on Lung Function in Healthy Elderly: Using Korean National Health and Nutrition Examination Survey.

Previous studies have demonstrated a positive association between obesity and decreased lung function. However, the effect of muscle and fat has not been fully assessed, especially in a healthy elderly population. In this study, we evaluated the impact of low muscle mass (LMM) and LMM with obesity on pulmonary impairment in healthy elderly subjects. Our study used data from the Korea National Health and Nutrition Examination Survey from 2008 to 2011. Men and women aged 65 yr or older were included. Muscle mass was measured by dual-energy X-ray absorptiometry. LMM was defined as two standard deviations below the sex-specific mean for young healthy adults. Obesity was defined as body mass index ≥ 25 kg/m(2). The prevalence of LMM in individuals aged over 65 was 11.9%. LMM and pulmonary function (forced vital capacity and forced expiratory volume in 1 second) were independently associated after adjusting for age, sex, body mass index, smoking status, alcohol consumption, and frequency of exercise. LMM with obesity was also related to a decrease in pulmonary function. This study revealed that LMM is an independent risk factor of decreased pulmonary function in healthy Korean men and women over 65 yr of age.

Relationship between Low Muscle Mass and Metabolic Syndrome in Elderly People with Normal Body Mass Index.

BACKGROUND: Metabolically obese normal weight (Wt) occurs in people who have high prevalence of cardiovascular disease even with normal body mass index (BMI). In this study, we determined the relationship between low muscle mass and metabolic syndrome which is known to be associated with cardiovascular disease in aged people with normal BMI. METHODS: This study used the data of Korea National Health and Nutrition Examination Survey. Aged people (≥ 65 years) with normal BMI (18.5 to 22.9 kg/m(2)) were enrolled. Low muscle mass class I was defined as appendicular skeletal muscle divided by Wt 1 to 2 standard deviation below the mean of gender specific young healthy adult and class II was defined as below 2 standard deviations. RESULTS: The prevalence of low muscle mass class I and II were 18.8% and 5.2% in men and 11.2% and 2.2% in women, respectively. In men and women, low muscle mass and metabolic syndrome was associated with each other after adjusting for age. After further adjusting for BMI, smoking status, alcohol consumption, and exercise frequency, the relationship was maintained in aged men. Moreover in aged men, the risk of metabolic syndrome was increased according to the grade increase in low muscle mass class. CONCLUSIONS: In the aged with normal BMI, low muscle mass was a risk factor of metabolic syndrome. Furthermore, in normal BMI men, when the degree of low muscle mass was enhanced, the risk of metabolic syndrome was increased.

Structures of iron-dependent alcohol dehydrogenase 2 from Zymomonas mobilis ZM4 with and without NAD+ cofactor.

The ethanologenic bacterium Zymomonas mobilis ZM4 is of special interest because it has a high ethanol yield. This is made possible by the two alcohol dehydrogenases (ADHs) present in Z. mobilis ZM4 (zmADHs), which shift the equilibrium of the reaction toward the synthesis of ethanol. They are metal-dependent enzymes: zinc for zmADH1 and iron for zmADH2. However, zmADH2 is inactivated by oxygen, thus implicating zmADH2 as the component of the cytosolic respiratory system in Z. mobilis. Here, we show crystal structures of zmADH2 in the form of an apo-enzyme and an NAD+­cofactor complex. The overall folding of the monomeric structure is very similar to those of other functionally related ADHs with structural variations around the probable substrate and NAD+ cofactor binding region. A dimeric structure is formed by the limited interactions between the two subunits with the bound NAD+ at the cleft formed along the domain interface. The catalytic iron ion binds near to the nicotinamide ring of NAD+, which is likely to restrict and locate the ethanol to the active site together with the oxidized Cys residue and several nonpolar bulky residues. The structures of the zmADH2 from the proficient ethanologenic bacterium Z. mobilis, with and without NAD+ cofactor, and modeling ethanol in the active site imply that there is a typical metal-dependent catalytic mechanism.

A case report of a chemical burn due to the misuse of glacial acetic acid.

As young and elastic skin is what everyone dreams of, various measures have been implemented including chemical, laser resurfacing and dermabrasion to improve the condition of ageing skin. However, the high cost of these procedures prevents the poor from having access to treatment. Glacial acetic acid is widely used as a substitute for chemical peeling because it is readily easily available and affordable. However, its use can result in a number of serious complications. A 28-year-old female patient was admitted to our hospital with deep second-degree chemical burns on her face caused by the application of a mixture of glacial acetic acid and flour for chemical peeling. During a 6-month follow-up, hypertrophic scarring developed on the both nasolabial folds despite scar management. Glacial acetic acid is a concentrated form of the organic acid, which gives vinegar its sour taste and pungent smell, and it is also an important reagent during the production of organic compounds. Unfortunately, misleading information regarding the use of glacial acetic acid for chemical peeling is causing serious chemical burns. Furthermore, there is high possibility of a poor prognosis, which includes inflammation, hypertrophic scar formation and pigmentation associated with its misuse. Therefore, we report a case of facial chemical burning, due to the misuse of glacial acetic acid, and hope that this report leads to a better understanding regarding the use of this reagent.

FAF1 suppresses IkappaB kinase (IKK) activation by disrupting the IKK complex assembly.

This study presents a molecular inhibitory mechanism by Fas-associated factor 1 (FAF1) on IkappaB kinase (IKK) activation, where divergent NF-kappaB-activating stimuli converge. FAF1 interacts with IKKbeta in response to proinflammatory stimuli (such as tumor necrosis factor-alpha, interleukin-1beta, and lipopolysaccharide) and suppresses IKK activation. Interaction of the leucine-zipper domain of IKKbeta with FAF1 affected the IKK heterocomplex (IKKalpha/beta) and homocomplex (IKKalpha/alpha, IKKbeta/beta) formations and attenuated IKKgamma recruitment to IKKbeta. Overexpression of FAF1 reduced the level of IKKbeta activity, whereas FAF1 depletion increased the activity. These results indicate that FAF1 inhibits IKK activation and its downstream signaling by interrupting the IKK complex assembly through physical interaction with IKKbeta. Taken together, FAF1 robustly suppresses NF-kappaB activation through the inhibition of IKK activation in combination with previously reported cytoplasmic retention of NF-kappaB p65 (Park, M. Y., Jang, H. D., Lee, S. Y., Lee, K. J., and Kim, E. (2004) J. Biol. Chem. 279, 2544-2549). Such redundant suppression would prevent inadvertent activation of the NF-kappaB pathway.