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1.
Ann Work Expo Health ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064494

RESUMO

OBJECTIVES: Polycyclic aromatic hydrocarbons (PAHs) are well-known carcinogens causing lung and skin cancers in exposed workers. Certain occupations, such as coke production, have been associated with high PAH exposure; however, the number of occupations tested to date remains small. Here, we sought to compare PAH exposure across a wide range of occupations based on levels of 1-hydroxypyrene (1-OHP), the urinary exposure surrogate of PAHs. METHODS: We collected urine 1-OHP data from the Korean National Environmental Health Survey (KoNEHS), a nationwide biomonitoring survey. We developed a linear regression model, controlling for sex, age, smoking, and survey cycle, and obtained resulting residuals. Then, we computed the fraction of exceeding the third quartile (Q3) level of residuals for each occupation, which is employed as a relative exposure indicator across occupations. RESULTS: A total of 15 125 measurements derived from three cycles of KoNEHS were used for analysis. The overall geometric means (GMs) and geometric standard deviation (GSD) of urine 1-OHP levels were 0.16 µg g-1 creatinine and 3.07, respectively. Among the sub-major occupational groups, 'construction and mining related elementary occupations' showed the highest fraction (0.45) of exceeding the Q3 level of residuals. Among the minor occupational groups, 'deliverers' showed a high fraction (0.42) of exceeding the Q3 level of residuals, which indicates rapidly growing occupations to be addressed. CONCLUSIONS: Our results provide ancillary information regarding PAH exposure across occupations, especially for occupations for which PAH exposure has not been well characterized.

2.
Sci Rep ; 10(1): 262, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937863

RESUMO

D-tyrosine is known to negatively regulate melanin synthesis by inhibiting tyrosinase activity. Here, we further reveal that peptides containing terminal D-tyrosine can reduce the melanin contents of human melanocytes. The addition of D-tyrosine to the terminus of the commercial anti-wrinkle peptide, pentapeptide-18 endowed the peptide with the ability to reduce the melanin content and tyrosinase activity in human MNT-1 melanoma cells and primary melanocytes. Consistently, terminal D-tyrosine-containing pentapeptide-18 inhibited the melanogenesis induced by α-MSH treatment or UV irradiation of MNT-1 cells and reduced melanin synthesis in the epidermal basal layer of a 3D human skin model. Furthermore, the addition of D-tyrosine to an anti-aging peptide (GEKG) or an anti-inflammatory peptide (GHK) endowed these short peptides with anti-melanogenic effects without altering their intrinsic effects. Together, these data suggest that the addition of D-tyrosine at the terminus of a short cosmetic peptide adds an anti-melanogenic effect to its intrinsic cosmetic effect. Our work offers a novel means of generating dual-function cosmetic peptides.

3.
Sci Rep ; 10(1): 1022, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974437

RESUMO

Chronic pruritus of unknown origin (CPUO) is defined as itching lasting more than 6 weeks in the absence of discernible skin lesions. Pregabalin is used to treat patients with CPUO. In this study, we aimed to investigate differences in the perception threshold of itch sensation between patients with CPUO and healthy individuals and to evaluate the efficacy of pregabalin for CPUO. At baseline, week 2, and week 4 after treatment initiation, the visual analogue scale (VAS) score was measured to assess pruritus severity, and electric current perception threshold (CPT) was measured at 250 and 5 Hz using a NEUROMETER CPT/C stimulator. Twenty healthy individuals and 41 patients with CPUO were enrolled in this study. The patients with CPUO were categorised as those who responded to antihistamines (Antihistamine group), were not improved by antihistamines (Pregabalin group), and were not improved by antihistamines and pregabalin (Refractory group). The baseline CPT values were not significantly different between patients with CPUO and healthy control. Pruritus was improved in 7 of 10 patients in the Pregabalin group after treatment with pregabalin, showing decreased CPT at 5 Hz. The sensitive C-fibres presented a high threshold to detect itch sensation, and this sensitivity decreased in response to treatment with pregabalin.

4.
Cell Signal ; 69: 109544, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31962151

RESUMO

Syndecans are single-pass transmembrane proteins on the cell surface that are involved in various cellular functions. Previously, we reported that both homo- and hetero-form of syndecan dimers affected their functionality. However, little is known about the structural role of the transmembrane domain of syndecan-3. A series of glutathione-S-transferase syndecan-3 proteins showed that syndecan-3 formed SDS-resistant dimers and oligomers. SDS-resistant oligomer formation was barely observed in the syndecan deletion mutants lacking the transmembrane domain. Interestingly, the presence of an alanine 397 residue in the transmembrane domain correlated with SDS-resistant oligomer, and its replacement by phenylalanine (AF mutant) significantly reduced SDS-resistant oligomer formation. Beside the AF mutant significantly reduced syndecan-3 mediated cellular processes such as cell adhesion, migration and neurite outgrowth of SH-SY5Y neuroblastoma. Furthermore, the alanine residue regulated hetero-oligomer formation of syndecan-3, and hetero-oligomer formation significantly reduced syndecan-3-mediated neurite outgrowth of SH-SY5Y cells. Taken together, all these data suggest that syndecan-3 has a specific feature of oligomerization by the transmembrane domain and this oligomerization tendency is crucial for the function of syndecan-3.

5.
J Microbiol ; 57(9): 781-794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452043

RESUMO

The phytopathogenic Burkholderia species B. glumae and B. plantarii are the causal agents of bacterial wilt, grain rot, and seedling blight, which threaten the rice industry globally. Toxoflavin and tropolone are produced by these phytopathogens and are considered the most hostile biohazards with a broad spectrum of target organisms. However, despite their nonspecific toxicity, the effects of toxoflavin and tropolone on bacteria remain unknown. RNA-seq based transcriptome analysis was employed to determine the genome-wide expression patterns under phytotoxin treatment. Expression of 2327 and 830 genes was differentially changed by toxoflavin and tropolone, respectively. Enriched biological pathways reflected the down-regulation of oxidative phosphorylation and ribosome function, beginning with the inhibition of membrane biosynthesis and nitrogen metabolism under oxidative stress or iron starvation. Conversely, several systems such as bacterial chemotaxis, flagellar assembly, biofilm formation, and sulfur/taurine transporters were highly expressed as countermeasures against the phytotoxins. In addition, our findings revealed that three hub genes commonly induced by both phytotoxins function as the siderophore enterobactin, an iron-chelator. Our study provides new insights into the effects of phytotoxins on bacteria for better understanding of the interactions between phytopathogens and other microorganisms. These data will also be applied as a valuable source in subsequent applications against phytotoxins, the major virulence factor.


Assuntos
Antibacterianos/toxicidade , Burkholderia/química , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Doenças das Plantas/microbiologia , Pirimidinonas/toxicidade , Triazinas/toxicidade , Tropolona/toxicidade , Antibacterianos/metabolismo , Burkholderia/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Oryza/microbiologia , Pirimidinonas/metabolismo , Transcriptoma/efeitos dos fármacos , Triazinas/metabolismo , Tropolona/metabolismo
6.
J Korean Med Sci ; 34(31): e213, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31392856

RESUMO

BACKGROUND: Tobacco smoking affects the incidence of various illnesses such as lung cancer, respiratory diseases, and cardiovascular diseases. In an effort to prevent smoking-related cancers, we aimed to estimate the smoking prevalence, intensity, and number of workers exposed to smoking, which would be specific to the occupational and industrial circumstances in Korea. METHODS: We used the Korean Working Condition Survey (KWCS) and Korea's Census data. Smoking prevalence and intensity were estimated using the KWCS data. The number of smokers was estimated by multiplying smoking prevalence with the number of workers in the occupation or industry. Smoking prevalence, intensity, and number of smokers were estimated for major, sub-major, and minor groups of occupation and industry. RESULTS: Of the total labor force in 2010, 52.66% of men and 5.24% of women workers were estimated to be current smokers. Men workers smoked 15.42 cigarettes/day, and women workers 11.29 cigarettes/day. In terms of occupation, "craft and related trades workers" demonstrated the highest smoking prevalence (52.24%). "Managers" smoked the highest number of cigarettes (16.63 cigarettes/day) and "equipment, machine operating, and assembling workers" comprised the largest number of estimated smokers (1,368,726 workers). In terms of industry, "mining and quarrying" had the highest smoking prevalence (69.27%). Those in "construction" smoked the highest number of cigarettes (17.16 cigarettes/day) and those in "manufacturing" comprised the largest number of estimated smokers (1,629,893 workers). CONCLUSION: Our results may help in setting priorities for smoking prevention-related activities. In addition, these results can be used for epidemiological studies controlling for the effect of smoking by occupation or industry.

7.
Can J Cardiol ; 35(5): 644-652, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31030865

RESUMO

BACKGROUND: Cardiovascular disease risk assessment tools help identify individuals likely to benefit from preventative therapies. In this study we compared outcomes using the American College of Cardiology/American Heart Association (ACC/AHA) risk algorithm and the Framingham Risk Score (FRS) tool in the Heart Outcomes Prevention Evaluation (HOPE)-3 study. METHODS: We compared outcomes using the ACC/AHA algorithm and the FRS with those seen in HOPE-3, which randomized participants to 10 mg rosuvastatin or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; second coprimary outcome additionally included heart failure, cardiac arrest, and revascularization. RESULTS: Relative risks using risk scores were similar to those observed in the HOPE-3. Hazards ratios for the first coprimary outcome according to risk categories of ≤ 10%, 10%-20%, and ≥ 20% using the ACC/AHA algorithm were 0.82 (95% confidence interval [CI], 0.53-1.28), 0.72 (95% CI, 0.53-0.96), and 0.72 (95% CI, 0.55-0.93), and absolute risk reduction (ARR) of 0.18%, 1.33%, and 1.85%, respectively, over a median of 5.6 years. Corresponding results using the FRS were 0.69 (95% CI, 0.36-1.35), 0.73 (95% CI, 0.52-1.01), and 0.75 (95% CI, 0.60- 0.94); and ARR of 1.32%, 0.61%, and 1.43%. Hazard ratios for the second coprimary outcome were 0.77 (95% CI, 0.51-1.14), 0.73 (95% CI, 0.56-0.95), and 0.74 (95% CI, 0.58-0.94); and ARR of 0.36%, 1.49%, and 1.85%, using the ACC/AHA algorithm and 0.76 (95% CI, 0.41-1.41), 0.70 (95% CI, 0.52-0.95), and 0.76 (95% CI, 0.62-0.94); and ARR of 1.08%, 0.83%, and 1.56% using the FRS. CONCLUSIONS: The pragmatic HOPE-3 trial approach identifies in an ethnically diverse primary prevention population individuals at intermediate risk who benefit from statin therapy using simple clinical characteristics without the need for complex, currently used risk assessment tools.

8.
Diabetes Obes Metab ; 21(6): 1502-1505, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30785660

RESUMO

The impact of insulin or omega-3 supplements on the incidence and progression of peripheral artery disease (PAD) in patients with dysglycaemia has not been well studied. The Outcome Reduction with an Initial Glargine INtervention (ORIGIN) trial randomized participants with dysglycaemia and cardiovascular risk factors to titrated insulin glargine vs standard care, and to either 1 g of omega-3 per day or placebo. We assessed incident PAD, defined as the composite of either asymptomatic or symptomatic PAD according to the randomized interventions in the 11 119 ORIGIN participants whose baseline ankle-brachial index (ABI) was >0.9 (no PAD), and PAD progression in the 971 ORIGIN participants whose baseline ABI was ≤0.9. Hazard ratios (HR) were adjusted for confounders. During a 6.2-year follow-up period, allocation to insulin glargine vs standard care had a neutral effect on the composite of PAD incidence (HR, 0.99; 95% CI, 0.86-1.15) and progression (HR, 0.88; 95% CI, 0.63-1.22). Similar findings were noted for allocation to omega-3 vs placebo for PAD incidence (HR, 1.02; 95% CI, 0.89-1.18) and progression (HR, 0.93; 95% CI, 0.67-1.28). In this large study, neither insulin glargine nor omega-3 affected the incidence or progression of PAD.

9.
Eur Heart J Qual Care Clin Outcomes ; 5(3): 266-271, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657891

RESUMO

AIMS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) found that rosuvastatin alone or with candesartan and hydrochlorothiazide (HCT) (in a subgroup with hypertension) significantly lowered cardiovascular events compared with placebo in 12 705 individuals from 21 countries at intermediate risk and without cardiovascular disease. We assessed the costs implications of implementation in primary prevention in countries at different economic levels. METHODS AND RESULTS: Hospitalizations, procedures, study and non-study medications were documented. We applied country-specific costs to the healthcare resources consumed for each patient. We calculated the average cost per patient in US dollars for the duration of the study (5.6 years). Sensitivity analyses were also performed with cheapest equivalent substitutes. The combination of rosuvastatin with candesartan/HCT reduced total costs and was a cost-saving strategy in United States, Canada, Europe, and Australia. In contrast, the treatments were more expensive in developing countries even when cheapest equivalent substitutes were used. After adjustment for gross domestic product (GDP), the costs of cheapest equivalent substitutes in proportion to the health care costs were higher in developing countries in comparison to developed countries. CONCLUSION: Rosuvastatin and candesartan/HCT in primary prevention is a cost-saving approach in developed countries, but not in developing countries as both drugs and their cheapest equivalent substitutes are relatively more expensive despite adjustment by GDP. Reductions in costs of these drugs in developing countries are essential to make statins and blood pressure lowering drugs affordable and ensure their use. CLINICAL TRIAL REGISTRATION: HOPE-3 ClinicalTrials.gov number, NCT00468923.

11.
Diabetes Care ; 42(1): 142-147, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30425095

RESUMO

OBJECTIVE: Epidemiological studies have reported a relationship between severe hypoglycemia, cognitive dysfunction, and dementia in middle-aged and older people with type 2 diabetes. However, whether severe or nonsevere hypoglycemia precedes cognitive dysfunction is unclear. Thus, the aim of this study was to analyze the relationship between hypoglycemia and incident cognitive dysfunction in a group of carefully followed patients using prospectively collected data in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. RESEARCH DESIGN AND METHODS: This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia who had additional cardiovascular risk factors and a Mini-Mental State Examination (MMSE) score ≥24 (N = 11,495). Severe and nonsevere hypoglycemic events were collected prospectively during a median follow-up time of 6.2 years. Incident cognitive dysfunction was defined as either reported dementia or an MMSE score of <24. The hazard of at least one episode of severe or nonsevere hypoglycemia for incident cognitive dysfunction (i.e., the dependent variable) from the time of randomization was estimated using a Cox proportional hazards model after adjusting for baseline cardiovascular disease, diabetes status, treatment allocation, and a propensity score for either form of hypoglycemia. RESULTS: This analysis did not demonstrate an association between severe hypoglycemia and incident cognitive impairment either before (hazard ratio [HR] 1.16; 95% CI 0.89, 1.52) or after (HR 1.00; 95% CI 0.76, 1.31) adjusting for the severe hypoglycemia propensities. Conversely, nonsevere hypoglycemia was inversely related to incident cognitive impairment both before (HR 0.59; 95% CI 0.52, 0.68) and after (HR 0.58; 95% CI 0.51, 0.67) adjustment. CONCLUSIONS: Hypoglycemia did not increase the risk of incident cognitive dysfunction in 11,495 middle-aged individuals with dysglycemia.


Assuntos
Doenças Cardiovasculares/epidemiologia , Disfunção Cognitiva/epidemiologia , Hipoglicemia/epidemiologia , Idoso , Doenças Cardiovasculares/sangue , Disfunção Cognitiva/sangue , Escolaridade , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Incidência , Insulina Glargina/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
12.
Eur J Prev Cardiol ; 26(7): 681-697, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30537846

RESUMO

BACKGROUND AND DESIGN: There are limited data on the effects of blood pressure and cholesterol lowering in Asians at intermediate risk and no cardiovascular disease. We report an analysis of the effects of blood pressure and cholesterol lowering in Asians enrolled in the Heart Outcomes Prevention Evaluation 3 (HOPE 3) trial. METHODS: We randomly assigned 6241 Asians and 6464 non-Asians at intermediate risk without cardiovascular disease to candesartan 16 mg/hydrochlorothiazide 12.5 mg or placebo and rosuvastatin 10 mg or placebo. The first co-primary outcome was a composite of cardiovascular disease death, myocardial infarction and stroke. The second co-primary outcome additionally included heart failure, cardiac arrest and revascularisation. Median follow-up was 5.6 years. RESULTS: Reduction in systolic blood pressure was less among Asians (4.3 vs. 7.7 mmHg for non-Asians, P < 0.0001) mainly due to a lesser effect in Chinese (2.1 mmHg) than in other Asians (7.3 mmHg), reduction in the latter being similar to non-Asians. The effect on the composite outcomes was similar, with no significant benefits from blood pressure lowering for either Asians (Chinese or non-Chinese) or non-Asians. Rosuvastatin reduced low-density lipoprotein cholesterol to a lesser degree in Asians (0.49 mmol/L (-19.1 mg/dL) compared with non-Asians 0.95 mmol/L (-36.7 mg/dL), Pinteraction < 0.0004). Yet both groups had similar reductions in the two co-primary outcomes. There was no increase in permanent medication discontinuation due to muscle-related symptoms in either group. There was an excess in new diabetes in non-Asians (4.70% rosuvastatin, 3.52% placebo, P = 0.025) but not in Asians (3.02% rosuvastatin, 4.04% placebo, P = 0.0342), Pinteraction = 0021. CONCLUSIONS: Candesartan/hydrochlorothiazide had fewer effects in reducing blood pressure in Chinese and rosuvastatin reduced low-density lipoprotein cholesterol to a lesser extent in Asians compared with non-Asians. There was no overall reduction in clinical events with lowering blood pressure in either Asians or non-Asians, whereas there were clear and consistent benefits with lipid lowering in both. Despite extensive analyses, we have no obvious explanation for the observed findings. Future studies need to include larger numbers of individuals from different regions of the world to ensure that the results of trials are applicable globally.

13.
Cell Signal ; 52: 121-126, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30195038

RESUMO

Cell surface receptors must specifically recognize an extracellular ligand and then trigger an appropriate response within the cell. Their general structure enables this, as it comprises an extracellular domain that can bind an extracellular ligand, a cytoplasmic domain that can transduce a signal inside the cell to produce an appropriate response, and a transmembrane domain that links the two and is responsible for accurately delivering specific information on a binding event from the extracellular domain to the cytoplasmic domain, to trigger the proper response. A vast body of research has focused on elucidating the specific mechanisms responsible for regulating extracellular binding events and the subsequent interactions of the cytoplasmic domain with intracellular signaling. In contrast, far less work has focused on examining how the transmembrane domain links these domains and delivers the necessary information. In this review, we propose the importance of the transmembrane domain as a signal regulator. We highlight the cell adhesion receptor, syndecan, as a special case, and propose that the transmembrane domain-mediated oligomerization of the syndecan cytoplasmic domain is a unique regulatory mechanism in syndecan signaling.


Assuntos
Membrana Celular/metabolismo , Receptores de Superfície Celular/química , Sindecanas/química , Animais , Adesão Celular , Humanos , Domínios Proteicos , Multimerização Proteica , Transdução de Sinais
14.
J Am Heart Assoc ; 7(15)2018 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-30033433

RESUMO

BACKGROUND: It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. METHODS AND RESULTS: In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with ≥2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73-1.00). Rosuvastatin reduced CVD events in participants with ≥2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62-0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61-1.01). Consistent results were observed with combination therapy (≥2 factors: HR: 0.74; 95% CI, 0.57-0.97; <2 factors: HR: 0.61; 95% CI, 0.43-0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61-1.00). CONCLUSIONS: Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00239681.


Assuntos
Benzimidazóis/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Estilo de Vida Saudável , Hidroclorotiazida/uso terapêutico , Prevenção Primária/métodos , Rosuvastatina Cálcica/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
15.
Biochem Biophys Res Commun ; 503(2): 615-620, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29902459

RESUMO

In human skin, melanocytes and their neighboring keratinocytes have a close functional interrelationship. Keratinocytes, which represent the prevalent cell type of human skin, regulate melanocytes through various mechanisms. Here, we use a keratinocyte and melanoma co-culture system to show for the first time that keratinocytes regulate the cell surface expression of N-cadherin through cell-cell contact. Compared to mono-cultured human melanoma A375 cells, which expressed high levels of N-cadherin, those co-cultured with the HaCaT human keratinocyte cell line showed reduced levels of N-cadherin. This reduction was most evident in areas of A375 cells that underwent cell-cell contact with the HaCaT cells, whereas HaCaT cell-derived extracellular matrix and conditioned medium both failed to reduce N-cadherin levels. The intracellular level of calcium in co-cultured A375 cells was lower than that in mono-cultured A375 cells, and treatment with a cell-permeant calcium chelator (BAPTA) reduced the N-cadherin level of mono-cultured A375 cells. Furthermore, co-culture with HaCaT cells reduced the expression levels of transient receptor potential cation channel (TRPC) 1, -3 and -6 in A375 cells, and siRNA-mediated multi-depletion of TRPC1, -3 and -6 reduced the N-cadherin level in these cells. Taken together, these data suggest that keratinocytes negatively regulate the N-cadherin levels of melanoma cells via cell-to-cell contact-mediated calcium regulation.


Assuntos
Caderinas/metabolismo , Cálcio/metabolismo , Comunicação Celular , Queratinócitos/patologia , Melanoma/patologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Queratinócitos/metabolismo , Melanoma/metabolismo , Camundongos , Canais de Cátion TRPC/metabolismo
16.
Ann Work Expo Health ; 62(2): 210-220, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29342235

RESUMO

Objective: Estimating carcinogen exposure prevalence is important for preventing occupational cancers. To develop the Korean version of CARcinogen EXposure (CAREX), a carcinogen surveillance system used in many countries, we estimated lead exposure prevalence in the Korean working population. Methods: We used three Korean nationwide data sources to obtain objective database-derived prevalences of lead exposure across industries: airborne lead measurement data from the work environment measurement database (WEMD), blood lead measurement data from the special health examination database (SHED), and lead exposure prevalence computed using data from the work environment condition survey (WECS), which is a nationwide occupational exposure survey. We also asked a panel of 52 experts with ≥20 years of experience in industrial hygiene practice for their judgment about lead exposure prevalence across industries after they reviewed the database-derived prevalences computed from the three exposure databases. We developed and compared various estimation methods for combining the experts' judgments. The 2010 census was used as the reference population to estimate the number of lead-exposed workers in 228 industries by multiplying the exposure prevalence by the number of workers in each industry. Results: The database-derived prevalences of lead exposure in the 228 industries were calculated using data collected between 2009 and 2011 from the WEMD and SHED and from the 2009 WECS. From the various estimation methods assessed, the median values of experts' responses were selected as our estimates of lead exposure prevalence in each industry. As a result, it was estimated that 129,250 Korean workers were exposed to lead in 2010. Conclusions: Based on objective databases, we developed a method for estimating exposure prevalence for the CAREX system by combining experts' judgments. This work may offer an unbiased approach to the development process that accounts for the uncertainty in exposure.


Assuntos
Poluentes Ocupacionais do Ar/análise , Carcinógenos/análise , Indústrias/estatística & dados numéricos , Chumbo/análise , Exposição Ocupacional/análise , Bases de Dados Factuais , Humanos , Chumbo/sangue , Exposição Ocupacional/estatística & dados numéricos , Saúde do Trabalhador/normas , Prevalência , Local de Trabalho/normas
17.
Pigment Cell Melanoma Res ; 31(3): 374-383, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29121440

RESUMO

Although L-tyrosine is well known for its melanogenic effect, the contribution of D-tyrosine to melanin synthesis was previously unexplored. Here, we reveal that, unlike L-tyrosine, D-tyrosine dose-dependently reduced the melanin contents of human MNT-1 melanoma cells and primary human melanocytes. In addition, 500 µM of D-tyrosine completely inhibited 10 µM L-tyrosine-induced melanogenesis, and both in vitro assays and L-DOPA staining MNT-1 cells showed that tyrosinase activity is reduced by D-tyrosine treatment. Thus, D-tyrosine appears to inhibit L-tyrosine-mediated melanogenesis by competitively inhibiting tyrosinase activity. Furthermore, we found that D-tyrosine inhibited melanogenesis induced by α-MSH treatment or UV irradiation, which are the most common environmental factors responsible for melanin synthesis. Finally, we confirmed that D-tyrosine reduced melanin synthesis in the epidermal basal layer of a 3D human skin model. Taken together, these data suggest that D-tyrosine negatively regulates melanin synthesis by inhibiting tyrosinase activity in melanocyte-derived cells.


Assuntos
Melaninas/biossíntese , Melanócitos/metabolismo , Melanoma/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Proteínas de Neoplasias/metabolismo , Tirosina/farmacologia , Linhagem Celular Tumoral , Humanos , Melanócitos/patologia , Melanoma/patologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Raios Ultravioleta
19.
Ann Work Expo Health ; 61(9): 1054-1075, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29136412

RESUMO

Objectives: CARcinogen EXposure (CAREX) is a carcinogen-surveillance system employed in many countries. To develop Korean CAREX, the intensity of exposure to lead, as an example, was estimated across industries. Methods: Airborne-lead measurement records were extracted from the work-environment measurement database (WEMD), which is a nationwide workplace-monitoring database. Lead measurements were log-transformed; then, the log-transformed geometric means (LGMs) and log-transformed geometric standard deviations (LGSDs) were calculated for each industry. However, the data of many industries was limited. To address this shortcoming, experts' judgments of the lead exposure levels across industries were elicited. Experts provided their estimates of lead exposure levels as the boundary of the 5th and 95th percentiles, and it is assumed that these estimates are based on the log-normal distributions of exposure levels. Estimates of LGM and LGSD were extracted from each expert's response and then combined to quantify the experts' prior distribution. Then, the experts' prior distributions for each industry were updated with the corresponding LGMs and LGSDs calculated from the WEMD data through a Bayesian framework, yielding posterior distributions of the LGM and LGSD. Results: The WEMD contains 83035 airborne-lead measurements that were collected between 2002 and 2007. A total of 17 occupational-hygiene professionals with >20 years of experience provided lead exposure estimates. In industries where measurement data were abundant, the measurement data dominated the posterior exposure estimates. For example, for one industry, 'Manufacture of Accumulator, Primary Cells, and Primary Batteries,' 1152 lead measurements [with a geometric mean (GM) of 14.42 µg m-3 and a geometric standard deviation (GSD) of 3.31] were available and 15 experts' responses (with a GM of 7.06 µg m-3 and a GSD of 4.15) were collected, resulting in a posterior exposure estimate of 14.41µg m-3 as the GM with a GSD of 3.31. For industries with a limited number of measurements available in the WEMD, experts' decisions played a significant role in determining the posterior exposure estimates. For example, for the 'Manufacture of Weapons and Ammunition' industry, 15 lead measurements (with a GM of 6.45 µg m-3 and a GSD of 3.37) were available and seven experts' responses (with a GM of 3.28 µg m-3 and a GSD of 4.54) were obtained, resulting in a posterior exposure estimate of 5.42 µg m-3 as the GM with a GSD of 3.73. Conclusions: The proposed method for estimating the intensity of exposure to carcinogens may introduce an unbiased approach to the development process by simultaneously utilizing both prior knowledge of experts and measurement data. In addition, it supplies a framework for future updates.


Assuntos
Poluentes Ocupacionais do Ar/análise , Carcinógenos/análise , Monitoramento Ambiental/métodos , Prova Pericial , Chumbo/análise , Modelos Teóricos , Exposição Ocupacional/análise , Agricultura , Teorema de Bayes , Humanos , Indústrias , Julgamento
20.
Diabetes Res Clin Pract ; 132: 137-143, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28837885

RESUMO

AIMS: To quantify whether insulin therapy, and concomitant weight gain, affects recreational physical activity and TV viewing time using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial. METHODS: 12,537 insulin-naïve individuals with dysglycaemia were randomised to receive either basal insulin glargine or standard care and followed for a median of 6.2years. Complete recreational physical activity and TV viewing time questionnaires across baseline, 2year follow-up and study end were available for 8954 participants. Differences between groups at follow-up were assessed by analysis of covariance. RESULTS: At follow-up, there was no difference in physical activity or TV viewing time between those taking insulin glargine and those receiving standard care, despite body weight increasing by 1.66 (7.56) kg in the insulin glargine group and reducing by -0.65 (7.90) kg in the standard care group (P<0.001). The dose of insulin glargine was not associated with changes in physical activity. CONCLUSIONS: Despite modest weight gain, insulin glargine did not adversely impact recreational physical activity levels within an international cohort with dysglyaemia. ORIGIN ClinicalTrials.gov number: NCT00069784.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Exercício/fisiologia , Insulina Glargina/uso terapêutico , Televisão/estatística & dados numéricos , Ganho de Peso/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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