A Newly Developed Indicator of Overeating Saturated Fat Based on Serum Fatty Acids and Amino Acids and Its Association With Incidence of Type 2 Diabetes: Evidence From Two Randomized Controlled Feeding Trials and a Prospective Study.

Objective: Hyper-caloric intake of saturated fatty acids (SFAs) is common in modern societies, probably contributing to the epidemic of type 2 diabetes mellitus (T2DM). This study conducted two randomized controlled trials (RCTs) for developing a new indicator that can assess the nutritional status and examined its association with incidence of T2DM. Methods: In RCT 1, healthy participants were randomly assigned into three groups, namely, control group (n = 40), overfeeding group 1 (100 g butter per day, n = 37), and overfeeding group 2 (120 g butter per day, n = 37). In RCT 2, healthy subjects were randomly assigned into two groups, namely, control group (n = 52) and high-fat group (300-extra kcal/day from diet that was designed by high-fat diet, n = 58). In the prospective cohort, 4,057 participants aged 20-74 years were enrolled and followed up over 5.3 years. Serum profiles of fatty acids and amino acids were measured. Results: In RCT 1, serum fatty acids, including C14:0 and C18:0, increased, whereas C18:2, C20:4, C22:5, and C22:6 decreased; serum amino acids, including tyrosine, alanine, and aminobutyric acid, increased, whereas histidine and glycine decreased (p < 0.05). Among these serum fatty acids and amino acids, changes in C14:0, C20:4, tyrosine, histidine, and glycine were also observed in RCT 2. An indicator was developed based on the five fatty acids and amino acids, namely, C14:0 × tyrosine × 1,000/[C20:4 × (glycine + histidine)], and it significantly identified participants in the intervention group with area under the curve (AUC) (95% CI) being 0.85 (0.77-0.92). The indicator was significantly associated with incidence of T2DM in the prospective cohort with HRs (95% CIs) from bottom quartile to top quartile being 1,1.21 (0.82-1.77), 1.60 (1.12-2.30), 2.04 (1.42-2.94). Conclusion: The newly developed indicator in RCTs can be used in assessing the nutritional status of hypercaloric intake of SFA and predicting the development of T2DM.

Fetal malnutrition is associated with impairment of endogenous melatonin synthesis in pineal via hypermethylation of promoters of protein kinase C alpha and cAMP response element-binding.

This study investigated whether and how fetal malnutrition would influence endogenous melatonin synthesis, and whether such effect of fetal malnutrition would transmit to the next generation. We enrolled 2466 participants and 1313 of their offspring. The urine 6-hydroxymelatonin sulfate and serum melatonin rhythm were measured. Methylation microarray detection and bioinformatics analysis were performed to identify hub methylated sites. Additionally, rat experiment was performed to elucidate mechanisms. The participants with fetal malnutrition had lower 6-hydroxymelatonin sulfate (16.59 ± 10.12 µg/24 hours vs 24.29 ± 11.99 µg/24 hours, P < .001) and arear under curve of melatonin rhythm (67.11 ± 8.16 pg/mL vs 77.11 ± 8.04 pg/mL, P < .001). We identified 961 differentially methylated sites, in which the hub methylated sites were locating on protein kinase C alpha (PRKCA) and cAMP response element-binding protein (CREB1) promoters, mediating the association of fetal malnutrition with impaired melatonin secretion. However, such effects were not observed in the offspring (all P > .05). Impaired histomorphology of pineal, decreased melatonin in serum, pineal, and pinealocyte were also found in the in vivo and in vitro experiments (P < .05 for the differences of the indicators). Hypermethylation of 10 CpG sites on the PRKCA promoter and 8 CpG sites on the CREB1 promoter were identified (all P < .05), which down-regulated PRKCA and CREB1 expressions, leading to decreased expression of AANAT, and then resulting in the impaired melatonin synthesis. Collectively, fetal malnutrition can impair melatonin synthesis through hypermethylation of PRKCA and CREB1 promoters, and such effects cannot be transmitted to the next generation.

Association of Meal and Snack Patterns With Mortality of All-Cause, Cardiovascular Disease, and Cancer: The US National Health and Nutrition Examination Survey, 2003 to 2014.

Background Although accumulating evidence has demonstrated that consumption time of energy and macronutrients plays an important role in maintaining health, the association between consumption time of different foods and cardiovascular disease, cancer, and all-cause mortalities is still largely unknown. Methods and Results A noninstitutionalized household population of the US 21 503 participants from National Health and Nutrition Examination Survey was included. Meal patterns and snack patterns throughout a whole day were measured using 24-hour dietary recall. Principal component analysis was performed to establish dietary patterns. Cox proportional hazards models were used to evaluate the association between dietary patterns across meals and cardiovascular disease (CVD), cancer, and all-cause mortalities. During the 149 875 person-years of follow-up, 2192 deaths including 676 deaths because of CVD and 476 because of cancer were documented. After adjusting for potential confounders, participants consuming fruit-lunch had lower mortality risks of all-cause (hazard ratio [HR], 0.82; 95% CI, 0.72-0.92) and CVD (HR, 0.66; 95% CI, 0.49-0.87); whereas participants who consumed Western-lunch were more likely to die because of CVD (HR, 1.44; 95% CI, 1.10-1.89). Participants who consumed vegetable-dinner had lower mortality risks of all-cause, CVD, and cancer (HRall-cause, 0.69; 95% CI, 0.60-0.78; HRCVD, 0.77; 95% CI, 0.61-0.95; HRcancer, 0.63; 95% CI, 0.48-0.83). For the snack patterns, participants who consumed fruit-snack after breakfast had lower mortality risks of all-cause and cancer (HRall-cause, 0.78; 95% CI, 0.66-0.93; HRcancer, 0.55; 95% CI, 0.39-0.78), and participants who consumed dairy-snack after dinner had lower risks of all-cause and CVD mortalities (HRall-cause, 0.82; 95% CI, 0.72-0.94; HRCVD, 0.67; 95% CI, 0.52-0.87). Participants who consumed a starchy-snack after main meals had greater mortality risks of all-cause (HRafter-breakfast, 1.50; 95% CI, 1.24-1.82; HRafter-lunch, 1.52; 95% CI, 1.27-1.81; HRafter-dinner, 1.50; 95% CI, 1.25-1.80) and CVD (HRafter-breakfast, 1.55; 95% CI, 1.08-2.24; HRafter-lunch, 1.44; 95% CI, 1.03-2.02; HRafter-dinner, 1.57; 95% CI, 1.10-2.23). Conclusions Fruit-snack after breakfast, fruit-lunch, vegetable-dinner, and dairy-snack after dinner was associated with lower mortality risks of CVD, cancer, and all-cause; whereas Western-lunch and starchy-snack after main meals had greater CVD and all-cause mortalities.

Third-hand smoke exposure is associated with abnormal serum melatonin level via hypomethylation of CYP1A2 promoter: Evidence from human and animal studies.

This study aimed to examine whether and how third-hand smoke (THS) exposure would influence serum melatonin level. 1083 participants with or without exposure to THS were enrolled. Serum ROS, SOD, GSH-Px, and melatonin were measured by ELISA. Methylation microarrays detection and WGCNA were performed to identify hub methylated-sites. The methylation levels of hub-sites were validated in addtional samples. Moreover, mice were exposed to THS for 6 months mimicking exposure of human and the serum, liver, and pineal were collected. Oxidative stress-related indicators in serum, pineal, and liver were measured by ELISA. The expressions of mRNA and protein and methylation levels of hub-gene discovered in human data were further explored by RT-PCR, western-blot, and TBS. The results showed the participants exposed to THS had lower melatonin-level. 820 differentially methylated sites associated with THS were identified. And the hub-site located on the CYP1A2 promoter was identified, which mediated the association between THS and decreased melatonin-level. Decreased peak of serum melatonin, increased ROS and reduced SOD and GSH-Px in pineal and liver, and elevated CYP1A2 expression in liver was also found in the THS-exposed mice. Hypo-methylation of 7 CPG sites on the CYP1A2 promoter was identified, which accelerated the catabolism of melatonin. Overall, THS exposure is associated with abnormal melatonin catabolism through hypo-methylation of CYP1A2-promoter.

Dibromoacetic acid exposure is associated with abnormal melatonin rhythm in rats via inhibition of p-CREB1-AANAT signalling pathway.

Dibromoacetic acid (DBA) is a by-product of disinfection in drinking water, which could cause many adverse effects in test animals. However, little research on its neurotoxicity has been conducted, and its mechanism has not been elucidated. In the present study, ninety Sprague-Dawley rats were administered DBA at doses of 0, 30, and 90 mg/kg body weight for 28 days via oral gavage. We found that DBA could induce obvious neurotoxicity in the pineal gland as indicated by histological changes and impaired rhythm of melatonin in pineal and serum. In the mechanism study, transcriptome data showed that DBA exposure could induce 732 differential expression genes. Besides, GO and KEGG analysis results indicated that these genes were enriched in circadian rhythms, among which CREB1 had the most significant fold change. And immunofluorescence staining (IF) and immunohistochemical staining (IHC) results showed that the number of amber-colored masculine neurons for the p-CREB1 in the 90 mg/kg group was markedly lower, and staining for the p-CREB1 was weaker. Moreover, the results of PCR and western blot showed that DBA exposure could down-regulate the expressions of CREB1 and p-CREB1, leading to the decreased expressions of gene and protein of arylalkylamine N-acetyltransferase (AANAT), and then resulting in the impaired melatonin synthesis in the pineal and serum. In conclusion, DBA exposure is associated with abnormal melatonin rhythm via inhibition of the p-CREB1-AANAT signalling pathway.

Are gastrointestinal and sleep problems associated with behavioral symptoms of autism spectrum disorder?

Many children with autism spectrum disorder (ASD) suffer from concurrent medical symptoms, including gastrointestinal (GI) and sleeping problems. However, there is limited information on the correlation between co-morbidities and autistic behavioral symptoms. In this study, we estimated the prevalence of GI and sleep problems in Chinese ASD children, examined the impacts of GI and sleep problems on autistic behavioral symptoms, and investigated the factors associated with GI and sleep problems. The survey included 169 ASD and 172 healthy children. Data regarding demographic characteristics, GI symptoms, sleep disturbances and behavioral symptoms were collected through questionnaires. GI and sleep problems were prevalent in Chinese ASD children. Moreover, ASD children with GI symptoms reported more severe ASD core symptoms than others. Autistic children's GI symptoms were associated with maternal sleep problems during pregnancy, child's 0-6 month food sources and picky eating. ASD children with sleep disturbances had lower performance in daily living skills, social cognition, social communication and intellectual development than ASD children without sleep disturbances. Sleep disturbances were associated with extra nutrient supply during lactation and feeding, and child's picky eating. Autistic children with GI or/and sleep problems may represent clinically relevant subtypes of ASD, for which targeted treatments may be needed.

Sialic acid and anti-ganglioside antibody levels in children with autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASD) may result from a combination of genetic and environmental factors, and impact neurological functions and behaviors. Sialic acid (SA) is an indispensable nutrient for early brain development, and its polymer polySia (PSA) can modify neural cell adhesion molecules (NCAM), thereby indirectly mediating neuronal outgrowth, synaptic connectivity and memory formation. To investigate the association between SA and ASD, we conducted a case-control study. METHODS: The study sample included 82 autistic children and 60 healthy children. We measured the levels of plasma SA and serum anti-gangliosides M1 antibodies (anti-GM1 antibodies) in the ASD and control groups. We also examined the severity of autistic children. RESULTS: The level of plasma SA in the control group was significantly higher than that in the ASD group (p < .01). Autistic children had higher positive rates of anti-GM1 antibodies (37.8%) than controls (21.67%, P = .04). However, there was no correlation between autistic severity and the levels of SA. SA may be as a biomarker for diagnosis of ASD with a positive predictive value of 84.42%, a negative predictive value of 73.85% and an area under the ROC curve value of 0.858. CONCLUSIONS: These results indicate that SA and anti-GM1 antibodies are associated with ASD. Our data suggested that future studies to explore the function of SA in the etiology of ASD may be needed.

[Therapeutic choices of penile erectile dysfunction].

OBJECTIVES: To discuss the therapeutic choices of erectile dysfunction (ED) and to improve the therapeutic efficacy for different ED cases. METHODS: Two hundred and twenty-seven patients with ED were treated repectively with psychological treatment(31 cases), oral testosterone(30 cases), Viagra(121 cases), psychological treatment + Viagra (16 cases), intraurethral PGE1 (8 cases) and intracavemous injection(21 cases). RESULTS: Among those ED patients, 142 (62.6%) cases reported improved erections after they had undergone above-mentioned therapies. The improved patients include 12 cases(38.7%) with psychological treatment, 9 cases (30.0%) with oral testosterone, 91 cases (75.2%) with Viagra, 13 cases (81.3%) with psychological and Viagar, 2 cases (25.0%) with intraurethral PGE1 and 21 cases (71.4%) with intracavemous injection. CONCLUSIONS: ED is a highly individualized disease, therapeutic choices of ED based on patient's situation can benefit those patients.

[Diagnostic approaches of neurogenic erectile dysfunction].

OBJECTIVES: To discuss the diagnostic approaches of neurogenic erectile dysfunction(ED), and to improve the diagnostic efficacy. METHODS: Two hundred and one patients with ED were evaluated by physical examination, IIEF-5, intracavernous injection, colour duplex ultrasonography and bulbocavernosus reflex latency, respectively. RESULTS: Among those ED patients, 173, 201, 106, 57 and 27 cases had undergone above-mentioned examines, 13 neurogenic ED and 188 miscellaneous(and unknown-causes) ED were diagnosed. CONCLUSIONS: Neurogenic erectile dysfunction is a common disorder, the diagnostic approaches should be based on patient's situation.