Serum Lipidome Signatures of Dogs with Different Endocrinopathies Associated with Hyperlipidemia

Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia) is a common finding in human and veterinary patients with endocrinopathies (e.g., hypothyroidism and hypercortisolism (Cushing’s syndrome; CS)). Despite emerging use of lipidomics technology in medicine, the lipid profiles of these endocrinopathies have not been evaluated and characterized in dogs. The aim of this study was to compare the serum lipidomes of dogs with naturally occurring CS or hypothyroidism with those of healthy dogs. Serum samples from 39 dogs with CS, 45 dogs with hypothyroidism, and 10 healthy beagle dogs were analyzed using a targeted lipidomics approach with liquid chromatography-mass spectrometry. There were significant differences between the lipidomes of dogs with CS, hypothyroidism, and the healthy dogs. The most significant changes were found in the lysophosphatidylcholines, lysophosphatidylethanolamines, lysophosphatidylinositols, phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, ceramides, and sphingosine 1-phosphates. Lipid alterations were especially pronounced in dogs with hypothyroidism. Several changes suggested a more atherogenic lipid profile in dogs with HT than in dogs with CS. In this study, we found so far unknown effects of naturally occurring hypothyroidism and CS on lipid metabolism in dogs. Our findings provide starting points to further examine differences in occurrence of atherosclerotic lesion formation between the two diseases

Moderate Alcohol Use and Mortality from Ischaemic Heart Disease: A Prospective Study in Older Chinese People

Abstract Background: Moderate alcohol use is generally associated with lower ischaemic heart disease (IHD) mortality but it is difficult to ascertain whether this is due to attributes of moderate alcohol users or the properties of alcohol itself. Evidence from populations with different patterns of alcohol use and IHD can provide crucial evidence. We assessed the association of moderate alcohol use with IHD mortality in older Chinese people from Hong Kong. Methodology We used Cox regression to determine whether moderate alcohol use was associated with IHD mortality in a prospective, population-based cohort study of all 56167 attendees, aged 65 years or over, from July 1998 to December 2000 at all 18 Elderly Health Centers operated by the Department of Health in Hong Kong. Principal Findings After a median follow-up of 4.2 years, there were 406 (188 in men, 218 in women) deaths from IHD in 54,090 subjects (96.3% successful follow-up). Moderate alcohol use in men was not associated with IHD mortality adjusted only for age [Hazard Ratio, HR 1.01 (95% CI 0.55 to 1.84) compared with never drinkers] or additionally adjusted for socioeconomic status and lifestyle. Almost all women were occasional drinkers and their current alcohol use was not significantly associated with IHD mortality [HR 0.88, (95% CI 0.51 to 1.53)]. Conclusions Moderate alcohol use had no effect on IHD mortality in older Chinese men. Lack of replication of the usual protective effect of moderate alcohol use in a setting with a different pattern of alcohol use and IHD could be due to chance or could suggest that the protective effect of alcohol on IHD does not extend to all populations

Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks

settings Open AccessArticle Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks by Nancy Lan Guo 1,*,Tuang Yeow Poh 2,Sandra Pirela 3,Mariana T. Farcas 4,Sanjay H. Chotirmall 2,Wai Kin Tham 5,Sunil S. Adav 5,Qing Ye 1,Yongyue Wei 6,Sipeng Shen 2,David C. Christiani 2,Kee Woei Ng 3,7,8,Treye Thomas 9,Yong Qian 4 andPhilip Demokritou 3 1 West Virginia University Cancer Institute/School of Public Health, West Virginia University, Morgantown, WV 26506, USA 2 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore 3 Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA 4 Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA 5 Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore 6 Key Lab for Modern Toxicology, Department of Epidemiology and Biostatistics and Ministry of Education (MOE), School of Public Health, Nanjing Medical University, Nanjing 210029, China 7 School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore 8 Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, Singapore 637141, Singapore 9 Office of Hazard Identification and Reduction, U.S. Consumer Product Safety Commission, Rockville, MD 20814, USA * Author to whom correspondence should be addressed. Int. J. Mol. Sci. 2019, 20(24), 6348; https://doi.org/10.3390/ijms20246348 Received: 2 December 2019 / Revised: 12 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019 (This article belongs to the Special Issue Advances in Nanostructured Materials between Pharmaceutics and Biomedicine) Download PDF Browse Figures Review Reports Cite This Paper Abstract Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model

Obesity, Physical Activity, and Mortality in a Prospective Chinese Elderly Cohort

Background In older people, it is unclear whether obesity relates to mortality, which calls into question its etiologic role in disease and its public health relevance. This apparent lack of relationship in older people could be an artifactual result of their diverse health states. Methods We used Cox regression analysis to determine whether the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) or physical activity on mortality varied with health status in a prospective cohort study of Chinese people 65 years or older enrolled from 1998 to 2000 at all of the 18 Elderly Health Centers of the Hong Kong Government Department of Health. Health status was categorized into 5 morbidity groups using a 12- item index covering illnesses, medications, frailty, and smoking. Results After a mean follow-up of 4.1 years, there were 3819 deaths in 54 088 subjects (96.5% successful followup). The effect of BMI on mortality varied with baseline health status (P_.001). In the healthiest group, obese people (BMI _25) had higher mortality (adjusted hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.02- 2.33), but in the unhealthiest group they had lower mortality (HR, 0.55; 95% CI, 0.49-0.63) compared with subjects of normal weight. Daily physical activity was associated with lower mortality compared with inactivity in the unhealthiest group (HR, 0.70; 95% CI, 0.61- 0.81) but not in the healthiest group. Conclusions In the elderly, the relationship between obesity and mortality varies according to the underlying health status. In those with poor health status, obesity is associated with better outcome, whereas in those with initially good health status, obesity is associated with worse outcome

In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/146540/1/12951_2018_Article_425.pd

Correction: Moderate Alcohol Use and Mortality from Ischaemic Heart Disease: A Prospective Study in Older Chinese People

Background: Moderate alcohol use is generally associated with lower ischaemic heart disease (IHD) mortality but it is difficult to ascertain whether this is due to attributes of moderate alcohol users or the properties of alcohol itself. Evidence from populations with different patterns of alcohol use and IHD can provide crucial evidence. We assessed the association of moderate alcohol use with IHD mortality in older Chinese people from Hong Kong. Methodology: We used Cox regression to determine whether moderate alcohol use was associated with IHD mortality in a prospective, population-based cohort study of all 56167 attendees, aged 65 years or over, from July 1998 to December 2000 at all 18 Elderly Health Centers operated by the Department of Health in Hong Kong. Principal Findings: After a median follow-up of 4.2 years, there were 406 (188 in men, 218 in women) deaths from IHD in 54,090 subjects (96.3 % successful follow-up). Moderate alcohol use in men was not associated with IHD mortality adjusted only for age [Hazard Ratio, HR 1.01 (95 % CI 0.55 to 1.84) compared with never drinkers] or additionally adjusted for socioeconomic status and lifestyle. Almost all women were occasional drinkers and their current alcohol use was not significantly associated with IHD mortality [HR 0.88, (95 % CI 0.51 to 1.53)]. Conclusions: Moderate alcohol use had no effect on IHD mortality in older Chinese men. Lack of replication of the usual protective effect of moderate alcohol use in a setting with a different pattern of alcohol use and IHD could be due to chanc

Smoking, quitting and mortality in an elderly cohort of 56 000 Hong Kong Chinese

Background: Although the harms of smoking are well established, it is unclear how they extend into old age in the Chinese. Aim: To examine the relationship of smoking with all-cause and major cause-specific mortality in elderly Chinese men and women, respectively, in Hong Kong. Methods: Mortality by smoking status was examined in a prospective cohort study of 56 167 (18 749 men, 37 416 women) Chinese aged ≥65 years enrolled from 1998 to 2000 at all the 18 elderly health centres of the Hong Kong Government Department of Health. Results: After a mean follow-up of 4.1 years, 1848 male and 2035 female deaths occured among 54 214 subjects (96.5% successful follow-up). At baseline, more men than women were current smokers (20.3% vs 4.0%) and former smokers (40.8% vs 7.9%). The adjusted RRs (95% Cl) for all-cause mortality in former and current smokers, compared with never smokers, were 1.39 (1.23 to 1.56) and 1.75 (1.53 to 2.00) in men and 1.43 (1.25 to 1.64) and 1.38 (1.14 to 1.68) in women, respectively. For current smokers, the RRs (95% Cl) for all-cause mortality were 1.59 (1.39 to 1.82), 1.72 (1.48 to 2.00) and 1.84 (1.43 to 2.35) for daily consumption of 1-9, 10-20 and >21 cigarettes, respectively (p for trend <0.001). RRs (95% Cl) were 1.49 (1.30 to 1.72) and 2.20 (1.88 to 2.57) in former and current smokers for all deaths from cancer, and 1.24 (1.04 to 1.47) and 1.57 (1.28 to 1.94) for all cardiovascular deaths, respectively. Quitters had significantly lower risks of death than current smokers from all causes, lung cancer, all cancers, stroke and all cardiovascular diseases. Conclusions: In old age, smoking continues to be a major cause of death, and quitting is beneficial. Smoking cessation is urgently needed in rapidly ageing populations in the East.published_or_final_versio

Association of plasma ceramide with decline in kidney function in patients with type 2 diabetes

Circulating ceramide levels are dysregulated in kidney disease. However, their associations with rapid decline in kidney function (RDKF) and end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) are unknown. In this prospective study of 1746 T2D participants, we examined the association of plasma ceramide Cer16:0, Cer18:0, Cer24:0, and Cer24:1 with RDKF, defined as an estimated glomerular filtration rate (eGFR) decline of 5 ml/min/1.73 m2 per year or greater, and ESKD defined as eGFR <15/min/1.73 m2 for at least 3 months, on dialysis or renal death at follow-up. During a median follow-up period of 7.7 years, 197 patients experienced RDKF. Ceramide Cer24:0 (odds ratio [OR] = 0.71, 95% CI 0.56–0.90) and ratios Cer16:0/Cer24:0 (OR = 3.54 [1.70–7.35]), Cer18:0/Cer24:0 (OR = 1.89 [1.10–3.25]), and Cer24:1/Cer24:0 (OR = 4.01 [1.93–8.31]) significantly associated with RDKF in multivariable analysis; 124 patients developed ESKD. The ratios Cer16:0/Cer24:0 (hazard ratio [HR] = 3.10 [1.44–6.64]) and Cer24:1/Cer24:0 (HR = 4.66 [1.93–11.24]) significantly associated with a higher risk of ESKD. The Cer24:1/Cer24:0 ratio improved risk discrimination for ESKD beyond traditional risk factors by small but statistically significant margin (Harrell C-index difference: 0.01; P = 0.022). A high ceramide risk score also associated with RDKF (OR = 2.28 [1.26–4.13]) compared to lower risk score. In conclusion, specific ceramide levels and their ratios are associated with RDKF and conferred an increased risk of ESKD, independently of traditional risk factors, including baseline renal functions in patients with T2D

Baseline characteristics of 54090 enrollees at Elderly Health Centres in Hong Kong from 1998 to 2000 with follow-up

<p>Baseline characteristics of 54090 enrollees at Elderly Health Centres in Hong Kong from 1998 to 2000 with follow-up</p

Hazard ratios with 95% confidence intervals for mortality from IHD and cancer of the esophagus by level of alcohol use in men and women

<p>Model 1 Adjusted for age group.</p><p>Model 2 Adjusted for age group, smoking status, education, housing, monthly expenditure, body mass index group and exercise.</p>*<p>All three current alcohol use groups were combined for women because of the small number of moderate and excessive drinkers in women.</p