Essential trace element and phosphatidylcholine remodeling: Implications for body composition and insulin resistance.

BACKGROUND: Recent studies indicated that bioactive lipids of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) predict unhealthy metabolic phenotypes, but results remain inconsistent. To fill this knowledge gap, we investigated whether essential trace elements affect PC-Lyso PC remodeling pathways and the risk of insulin resistance (IR). METHODS: Anthropometric and blood biochemical data (glucose, insulin, and lipoprotein-associated phospholipase A2 (Lp-PLA2)) were obtained from 99 adults. Blood essential/probably essential trace elements and lipid metabolites were respectively measured by inductively coupled plasma mass spectrometry (ICP-MS), and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULT AND CONCLUSION: Except for LysoPC (O-18:0/0:0), an inverse V shape was observed between body weight and PC and LysoPC species. A Pearson correlation analysis showed that essential/probably-essential metals (Se, Cu, and Ni: r=-0.4∼-0.7) were negatively correlated with PC metabolites but positively correlated with LysoPC (O-18:0/0:0) (Se, Cu, and Ni: r=0.85-0.64). Quantile-g computation showed that one quantile increase in essential metals was associated with a 2.16-fold increase in serum Lp-PLA2 (ß=2.16 (95 % confidence interval (CI): 0.34, 3.98), p=0.023), which are key enzymes involved in PC/Lyso PC metabolism. An interactive analysis showed that compared to those with the lowest levels (reference), individuals with the highest levels of serum PCs (pooled, M2) and the lowest essential/probably essential metals (M1) were associated with a healthier body composition and had a 76 % decreased risk of IR (odds ratio (OR)=0.24 (95 % CI: 0.06, 0.90), p<0.05). In contrast, increased exposure to LysoPC(O-18:0/0:0) (M2) and essential metals (M2) exhibited an 8.22-times highest risk of IR (OR= 8.22 (2.07, 32.57), p<0.05) as well as an altered body composition. In conclusion, overexposure to essential/probably essential trace elements may promote an unhealthy body weight and IR through modulating PC/LysoPC remodeling pathways.

Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Sleep deprivation alters pubertal timing in humans and rats: the role of the gut microbiome.

STUDY OBJECTIVES: Evidence implied that sleeping duration is associated with the timing of puberty and that sleep deprivation triggers early pubertal onset in adolescents. Sleep deprivation can affect metabolic changes and gut microbiota composition. This study investigated the effects of sleep deprivation on pubertal onset and gut microbiota composition in animal models and a human cohort. METHODS: This study comprised 459 boys and 959 girls from the Taiwan Pubertal Longitudinal Study. Sleep duration was evaluated using the self-report Pittsburgh Sleep Quality Index questionnaire. Early sexual maturation was defined by pediatric endocrinologist assessments. Mediation analyses were done to examine the association between sleep parameters, obesity, and early sexual maturation. Besides, Sprague Dawley juvenile rats were exposed to 4 weeks of chronic sleep deprivation. Vaginal opening (VO) and preputial separation (PS) were observed every morning to determine pubertal onset in female and male rats. RESULTS: The sleep-deprived juvenile rats in the sleep-deprived-female (SDF) and sleep-deprived-male (SDM) groups experienced delayed VO (mean VO days: 33 days in control; 35 days in SDF; p-value < 0.05) and PS (mean PS days: 42 days in control; 45 days in SDM; p-value < 0.05), respectively. Relative to their non-sleep-deprived counterparts, the sleep-deprived juvenile rats exhibited lower body weight and body fat percentage. Significant differences in relative bacterial abundance at genus levels and decreased fecal short-chain-fatty-acid levels were identified in both the SDF and SDM groups. In the human cohort, insufficient sleep increased the risk of early sexual maturation, particularly in girls (OR, 1.44; 95% CI: 1.09 to 1.89; p-value < 0.01). Insufficient sleep also indirectly affected early sexual maturation in girls, with obesity serving as the mediator. CONCLUSIONS: Overall, sleep deprivation altered the timing of puberty in both animal and human models but in different directions. In the rat model, sleep deprivation delayed the pubertal onset in juvenile rats through gut dysbiosis and metabolic changes, leading to a low body weight and body fat percentage. In the human model, sleep deprivation led to fat accumulation, causing obesity in girls, which increased the risk of early puberty.

Melatonin Ameliorates Neuropsychiatric Behaviors, Gut Microbiome, and Microbiota-Derived Metabolites in Rats with Chronic Sleep Deprivation.

With the increasing prevalence of sleep deprivation (SD)-related disorders, the effective treatment of sleep disorders has become a critical health research topic. Thus, we hypothesized and investigated the effectiveness of a 3-week melatonin intervention on neuropsychiatric behavioral responses mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD. Eighteen 6-week-old Wistar rats were used and divided into the control grup (C, n = 6), SD group (n = 6), and melatonin-supplemented group (SDM, n = 6). During weeks 0 to 6, animals were provided with the AIN-93M diet and free access to water. Four-week chronic SD was conducted from weeks 7 to 10. Exogenous melatonin administration (10 mg/kg BW) was injected intraperitoneally 1 h before the daily administration of SD for 3 weeks in the SDM group. SD rats exhibited anxiety-like behavior, depression-like behavior, and cognitive impairment. Exogenous melatonin administration ameliorated neuropsychiatric behaviors induced by chronic SD. Analysis of fecal metabolites indicated that melatonin may influence brain messaging through the microbiota-gut-brain axis by increasing the production of short-chain fatty acids (SCFA) and decreasing the production of secondary bile acids (SBA). Four-week SD reduced the cerebral cortex expression of MT1, but not in the colon. Chronic SD led to anxiety and depression-like behaviors and cognitive decline, as well as the reduced intestinal level of SCFAs and the enhanced intestinal level of SBAs in rats. In this work, we confirmed our hypothesis that a 3-week melatonin intervention on neuropsychiatric behavioral response mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD.

Roles of Omega-3 Polyunsaturated Fatty Acids in Managing Cognitive Impairment in Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease (COPD) contributes significantly to the death of people worldwide, especially the elderly. An essential feature of COPD is pulmonary inflammation, which results from long-term exposure to noxious substances from cigarette smoking and other environmental pollutants. Pulmonary inflammatory mediators spill over to the blood, leading to systemic inflammation, which is believed to play a significant role in the onset of a host of comorbidities associated with COPD. A substantial comorbidity of concern in COPD patients that is often overlooked in COPD management is cognitive impairment. The exact pathophysiology of cognitive impairment in COPD patients remains a mystery; however, hypoxia, oxidative stress, systemic inflammation, and cerebral manifestations of these conditions are believed to play crucial roles. Furthermore, the use of medications to treat cognitive impairment symptomatology in COPD patients has been reported to be associated with life-threatening adverse effects, hence the need for alternative medications with reduced side effects. In this Review, we aim to discuss the impact of cognitive impairment in COPD management and the potential mechanisms associated with increased risk of cognitive impairment in COPD patients. The promising roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in improving cognitive deficits in COPD patients are also discussed. Interestingly, ω-3 PUFAs can potentially enhance the cognitive impairment symptomatology associated with COPD because they can modulate inflammatory processes, activate the antioxidant defence system, and promote amyloid-beta clearance from the brain. Thus, clinical studies are crucial to assess the efficacy of ω-3 PUFAs in managing cognitive impairment in COPD patients.

Attenuation of Chronic Stress-Induced Depressive-like Symptoms by Fish Oil via Alleviating Neuroinflammation and Impaired Tryptophan Metabolism in Aging Rats.

The prevalence of depression is increasing, and geriatric depression, in particular, is difficult to recognize and treat. Depression in older adults is often accompanied by neuroinflammation in the central nervous system (CNS). Neuroinflammation affects the brain's physiological and immune functions through several pathways and induces depressive symptoms. This study investigated the relationship among depression, neuroinflammation, and fish oil supplementation. Thirty-six male Sprague-Dawley rats were used in an aging-related depression animal model to simulate geriatric depression. Cognitive function, depressive-like symptoms, peripheral nervous system and CNS inflammation status, and the tryptophan-related metabolic pathway were analyzed. The geriatric depression animal model was associated with depressive-like behaviors and cognitive impairment. The integrity of the blood-brain barrier was compromised, resulting in increased expression of ionized calcium-binding adapter molecule 1 and the glial fibrillary acidic protein in the brain, indicating increased neuroinflammation. Tryptophan metabolism was also negatively affected. The geriatric-depressive-like rats had high levels of neurotoxic 5-hydroxyindoleacetic acid and kynurenine in their hippocampus. Fish oil intake improved depressive-like symptoms and cognitive impairment, reduced proinflammatory cytokine expression, activated the brain's glial cells, and increased the interleukin-10 level in the prefrontal cortex. Thus, fish oil intervention could ameliorate abnormal neurobehaviors and neuroinflammation and elevate the serotonin level in the hippocampus.

Modulatory effect of n-3 polyunsaturated fatty acids on depressive-like behaviors in rats with chronic sleep deprivation: potential involvement of melatonin receptor pathway and brain lipidome.

Clinical evidence suggests that a bidirectional relationship is present between sleep loss and psychiatric disorders. Both melatonin receptor agonist ramelteon (RMT) and n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit antidepressant effects, while their underlying molecular mechanisms might be different. Thus, the present study aims to investigate the add-on effects and possible mechanisms of how RMT and different n-3 PUFAs modulate the melatonin receptor pathway as well as brain lipidome to ameliorate the neuropsychiatric behaviors displayed in rats under chronic sleep deprivation. Thirty-one 6-week-old male Wistar rats were divided into five groups: control (C), sleep deprivation (S), sleep deprivation treated with RMT (SR), sleep deprivation treated with RMT and eicosapentaenoic acid (C20:5n-3, EPA) (SRE), and sleep deprivation treated with RMT and docosahexaenoic acid (C22:6n-3, DHA) (SRD) groups. The results reveal that RMT plus EPA alleviated depressive-like behavior when the rats were subjected to the forced swimming test, whereas RMT plus DHA alleviated anxiety-like behavior when the rats were subjected to the elevated plus maze test. The results of a western blot analysis further revealed that compared with the rats in the S group, those in the SRE and SRD groups exhibited a significantly increased expression of MT2 in the prefrontal cortex, with greater benefits observed in the SRE group. In addition, decreased BDNF and TrkB expression levels were upregulated only in the SRE group. Lipidomic analysis further revealed possible involvement of aberrant lipid metabolism and neuropsychiatric behaviors. RMT plus EPA demonstrated promise as having the effects of reversing the levels of the potential biomarkers of depressive-like behaviors. RMT plus EPA or DHA could ameliorate depressive- and anxiety-like behaviors in sleep-deprived rats through the alteration of the lipidome and MT2 receptor pathway in the brain, whereas EPA and DHA exerted a differential effect.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), somatic and fatigue symptoms in cardiovascular diseases comorbid major depressive disorder (MDD): A randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVDs) and major depressive disorder (MDD) are the two most disabling diseases. Patients with CVDs comorbid depression had somatic and fatigue symptoms and were associated with chronic inflammation and omega-3 polyunsaturated fatty acid (n-3 PUFA) deficits. However, there have been limited studies on the effects of n-3 PUFAs on somatic and fatigue symptoms in patients with CVDs comorbid MDD. METHOD: Forty patients with CVDs comorbid MDD (58% males, mean age of 60 ± 9 years) were enrolled and randomised to receive either n-3 PUFAs (2 g of eicosapentaenoic acid [EPA] and 1 g of docosahexaenoic acid[DHA] per day) or placebo in a 12-week double-blind clinical trial. We assessed the somatic symptoms with Neurotoxicity Rating Scale (NRS) and fatigue symptoms with Fatigue Scale at baseline, weeks 1, 2, 4, 8 and 12, as well as blood levels of Brain-Derived Neurotrophic Factor (BDNF), inflammatory biomarkers and PUFAs, at the baseline and week 12. RESULTS: The n-3 PUFAs group had a greater reduction in Fatigue scores than the placebo group at Week 4 (p =.042), while there were no differences in the changes of NRS scores. N-3 PUFAs group also had a greater increase in EPA (p =.001) and a greater decrease in total n-6 PUFAs (p =.030). Moreover, in the subgroup analyses in the younger age group (age < 55), the n-3 PUFAs group had a greater reduction on NRS total scores at Week 12 (p =.012) and NRS Somatic scores at Week 2 (p =.010), Week 8 (p =.027), Week 12 (p =.012) than the placebo group. In addition, the pre- and post-treatment changes of EPA and total n-3 PUFAs levels were negatively associated with the changes of NRS scores at Weeks 2, 4, and 8 (all p <.05), and the changes of BDNF levels were negatively associated with NRS scores at Weeks 8 and 12 (both p <.05) in the younger age group. In the older age group (age ≥ 55), there were a lesser reduction on NRS scores at Weeks 1, 2 and 4 (all p <.05), but a greater reduction on Fatigue score at Week 4 (p =.026), compared to the placebo group. There was no significant correlation between the changes of blood BDNF, inflammation, PUFAs and NRS and Fatigue scores in general and in the older age group. CONCLUSION: Overall, n-3 PUFAs improved the fatigue symptoms in patients with CVDs comorbid MDD and the general somatic symptoms in specific subpopulation of younger age patients, and perhaps via the interplay between BDNF and EPA. Our findings provide promising rationales for future studies to investigate the treatment effects of omega-3 fatty acids on fatigue and somatic symptoms of chronic mental and medical diseases.

Maternal Omega-3 Supplementation During Pregnancy, but Not Childhood Supplementation, Reduces the Risk of Food Allergy Diseases in Offspring.

BACKGROUND: Omega-3 supplementation has been reported to modulate immune responses and prevent food allergies among children; however, findings are inconsistent, and the timing of supplementation, which is critical, has not been thoroughly investigated. OBJECTIVE: To assess optimal timing (maternal vs childhood intake) of omega-3 supplementation for reducing food allergy risk among children in 2 periods (the first 3 years and beyond 3 years of age). METHODS: We performed a meta-analysis to assess the effects of maternal or childhood omega-3 supplementation on preventing the development of infant food allergies and food sensitizations. The PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were searched for related studies published until October 30, 2022. We conducted dose-response and subgroup analyses to investigate the effects of omega-3 supplementation. RESULTS: We found that maternal omega-3 supplementation during pregnancy and lactation was significantly associated with decreased risks of infant egg sensitization (relative risk [RR]: 0.58, 95% confidence interval [95% CI]: 0.47-0.73, P < .01) and peanut sensitization (RR: 0.62, 95% CI: 0.47-0.80, P < .01) among children. Similar results were found in subgroup analyses for food allergy, egg sensitization, and peanut sensitization during the first 3 years of age and peanut sensitization and cashew nut sensitization beyond 3 years of age. Dose-response analysis showed a linear relationship between maternal omega-3 supplementation and infant egg sensitization risk during early life. By contrast, intake of omega-3 polyunsaturated fatty acid during childhood did not appear to significantly protect against food allergies. CONCLUSIONS: Maternal omega-3 supplementation during pregnancy and lactation, rather than childhood intake, reduces the risk of infant food allergy and food sensitization.

Potential Hepatic Lipid Markers Associated with Nonalcoholic Steatohepatitis and Fibrosis in Morbid Obesity Patients.

This study investigated differences in lipidomic profile features in nonalcoholic steatohepatitis (NASH) between mild and significant liver fibrosis cases among patients with morbid obesity. Wedge liver biopsy was performed during sleeve gastrectomy and significant liver fibrosis was defined as a fibrosis score ≥ 2. We selected patients with NASH with non/mild fibrosis (stage F0-F1; n = 30) and NASH with significant fibrosis (stage F2-F4; n = 30). The results of the liver tissue lipidomic analysis revealed that the fold changes of triglyceride (TG) (52:6); cholesterol ester (CE) (20:1); phosphatidylcholine (PC) (38:0) and (50:8); phosphatidic acid (PA) (40:4); phosphatidylinositol (PI) (49:4); phosphatidylglycerol (PG) (40:2); and sphingomyelin (SM) (35:0) and (37:0) were significantly lower in patients with NASH with F2-F4 than those with NASH with F0-F1 (p < 0.05). However, the fold changes of PC (42:4) were relatively higher in patients with NASH with stage 2-4 fibrosis (p < 0.05). Moreover, predictive models incorporating serum markers levels, ultrasonographic studies, and levels of specific lipid components [PC (42:4) and PG (40:2)] yielded the highest area under receiver operating curve (0.941), suggesting a potential correlation between NASH fibrosis stages and liver lipid accumulation among specific lipid species subclasses. This study demonstrated that the concentrations of particular lipid species in the liver correlate with NASH fibrosis stages and may indicate hepatic steatosis regression or progression in patients with morbid obesity.

Omega-3 Polyunsaturated Fatty Acids in Managing Comorbid Mood Disorders in Chronic Obstructive Pulmonary Disease (COPD): A Review.

Chronic obstructive pulmonary disease (COPD) is the third-leading cause of mortality globally, significantly affecting people over 40 years old. COPD is often comorbid with mood disorders; however, they are frequently neglected or undiagnosed in COPD management, thus resulting in unintended treatment outcomes and higher mortality associated with the disease. Although the exact link between COPD and mood disorders remains to be ascertained, there is a broader opinion that inflammatory reactions in the lungs, blood, and inflammation-induced changes in the brain could orchestrate the onset of mood disorders in COPD. Although the current management of mood disorders such as depression in COPD involves using antidepressants, their use has been limited due to tolerability issues. On the other hand, as omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a vital role in regulating inflammatory responses, they could be promising alternatives in managing mood disorders in COPD. This review discusses comorbid mood disorders in COPD as well as their influence on the progression and management of COPD. The underlying mechanisms of comorbid mood disorders in COPD will also be discussed, along with the potential role of n-3 PUFAs in managing these conditions.

Effects of Resveratrol on Muscle Inflammation, Energy Utilisation, and Exercise Performance in an Eccentric Contraction Exercise Mouse Model.

Eccentric contraction can easily cause muscle damage and an inflammatory response, which reduces the efficiency of muscle contraction. Resveratrol causes anti-inflammatory effects in muscles, accelerates muscle repair, and promotes exercise performance after contusion recovery. However, whether resveratrol provides the same benefits for sports injuries caused by eccentric contraction is unknown. Thus, we explored the effects of resveratrol on inflammation and energy metabolism. In this study, mice were divided into four groups: a control group, an exercise group (EX), an exercise with low-dose resveratrol group (EX + RES25), and an exercise with high-dose resveratrol group (EX + RES150). The results of an exhaustion test showed that the time before exhaustion of the EX + RES150 group was greater than that of the EX group. Tumour necrosis factor-α (Tnfα) mRNA expression was lower in the EX + RES150 group than in the EX group. The energy utilisation of the EX + RES150 group was greater than that of the EX + RES25 group in different muscles. High-dose resveratrol intervention decreased Tnfα mRNA expression and enhanced the mRNA expressions of sirtuin 1, glucose transporter 4, AMP-activated protein kinase α1, and AMP-activated protein kinase α2 in muscles. These results revealed that high-dose resveratrol supplementation can reduce inflammation and oxidation and improve energy utilisation during short-duration high-intensity exercise.

Aspartame consumption during pregnancy impairs placenta growth in mice through sweet taste receptor-reactive oxygen species-dependent pathway.

The prevalence of obesity has risen dramatically over recent years, and so has the prevalence of adverse obesity-associated pregnancy outcomes. To combat obesity, the calorie contents of many foods and beverages may be reduced by the use of artificial sweeteners, such as aspartame. However, animal studies suggest that aspartame and its metabolites may exhibit toxicity, and the effects of aspartame on pregnancy are largely unknown. In this study, we treated pregnant mice with aspartame by oral gavage and found that the treatment decreased fasting blood glucose level, whereas systolic blood pressure was elevated. Importantly, the aspartame-treated animals also had low placenta and fetus weights, as well as reduced thickness of the placenta decidua layer. Moreover, aspartame decreased the expression of epithelial-mesenchymal transition proteins and manganese superoxide dismutase (MnSOD) in mouse placentae. In order to clarify the mechanisms though which aspartame affects placenta, we performed experiments on 3A-sub-E trophoblasts. In the cells, aspartame treatments induced cell cycle arrest and reduced the proliferation rate, epithelial-mesenchymal transition, migration activity and invasion activity. We also found that aspartame increased reactive oxygen species (ROS) levels to hyper-activate Akt and downregulate MnSOD expression. Pretreatment with antioxidants or sweet taste receptor inhibitors reversed the effects of aspartame on trophoblast function. We also found that the aspartame metabolite phenylalanine similarly induced ROS production and affected proliferation of trophoblasts. Taken together, our data suggest that aspartame consumption during pregnancy may impact the structure, growth and function of the placenta via sweet taste receptor-mediated stimulation of oxidative stress.

Yohimbine, an α2-Adrenoceptor Antagonist, Suppresses PDGF-BB-Stimulated Vascular Smooth Muscle Cell Proliferation by Downregulating the PLCγ1 Signaling Pathway.

Yohimbine (YOH) has antiproliferative effects against breast cancer and pancreatic cancer; however, its effects on vascular proliferative diseases such as atherosclerosis remain unknown. Accordingly, we investigated the inhibitory mechanisms of YOH in vascular smooth muscle cells (VSMCs) stimulated by platelet-derived growth factor (PDGF)-BB, a major mitogenic factor in vascular diseases. YOH (5-20 µM) suppressed PDGF-BB-stimulated a mouse VSMC line (MOVAS-1 cell) proliferation without inducing cytotoxicity. YOH also exhibited antimigratory effects and downregulated matrix metalloproteinase-2 and -9 expression in PDGF-BB-stimulated MOVAS-1 cells. It also promoted cell cycle arrest in the initial gap/first gap phase by upregulating p27Kip1 and p53 expression and reducing cyclin-dependent kinase 2 and proliferating cell nuclear antigen expression. We noted phospholipase C-γ1 (PLCγ1) but not ERK1/2, AKT, or p38 kinase phosphorylation attenuation in YOH-modulated PDGF-BB-propagated signaling pathways in the MOVAS-1 cells. Furthermore, YOH still inhibited PDGF-BB-induced cell proliferation and PLCγ1 phosphorylation in MOVAS-1 cells with α2B-adrenergic receptor knockdown. YOH (5 and 10 mg/kg) substantially suppressed neointimal hyperplasia in mice subjected to CCA ligation for 21 days. Overall, our results reveal that YOH attenuates PDGF-BB-stimulated VSMC proliferation and migration by downregulating a α2B-adrenergic receptor-independent PLCγ1 pathway and reduces neointimal formation in vivo. Therefore, YOH has potential for repurposing for treating atherosclerosis and other vascular proliferative diseases.

N-3 PUFA Ameliorates the Gut Microbiota, Bile Acid Profiles, and Neuropsychiatric Behaviours in a Rat Model of Geriatric Depression.

The brain-gut-microbiome (BGM) axis affects host bioinformation. N-3 polyunsaturated fatty acids (PUFAs) alleviate cognitive impairment and depression in older adults. This study investigated altered microbiota-bile acid signalling as a potential mechanism linking fish oil-induced gut changes in microbiota to alleviate psychological symptoms. Sprague Dawley rats were fed a fish oil diet and administered D-galactose combined with chronic unpredictable mild stress (CUMS) to simulate geriatric depression. The cognitive function, psychological symptoms, microbiota compositions, and faecal bile acid profiles of the rats were assessed thereafter. A correlation analysis was conducted to determine whether the fish oil-induced alteration of the rats' microbiota and bile acid profiles affected the rats' behaviour. D-galactose and CUMS resulted in lower concentrations of Firmicutes, significantly altered bile acid profiles, and abnormal neurobehaviours. Fish oil intake alleviated the rats' emotional symptoms and increased the abundance of Bacteroidetes, Prevotellaceae, Marinifilaceae, and Bacteroidesuniformis. It also elevated the concentrations of primary bile acids and taurine-conjugated bile acids in the rats' faeces. The rats' taurine-conjugated bile acid levels were significantly correlated with their behavioural outcomes. In short, fish oil intake may alleviate psychological symptoms by altering the microbial metabolites involved in the BGM axis, especially in the conjugation of bile acids.

Pathological brain lesions in girls with central precocious puberty at initial diagnosis in Southern Vietnam.

PURPOSE: Cranial magnetic resonance imaging (MRI) is recommended to identify intracranial lesions in girls with central precocious puberty (CPP). Yet, the use of routine MRI scans in girls with CPP is still debatable, as pathological findings in girls 6 years of age or older with CPP are limited. Therefore, we aimed to identify the prevalence of brain lessons in CPP patients stratified by age group (0-2, 2-6, and 6-8 years). METHODS: This retrospective cross-sectional study recruited 257 girls diagnosed with CPP for 6 years (2010-2016). MRI was used to detect brain abnormalities. Levels of luteinizing hormone, follicle-stimulating hormone, and sex hormones in blood samples were measured. RESULTS: Most girls had no brain lesions (82.9%, n=213), and of the minor proportion of girls with CPP that exhibited brain lesions (17.1%, n=44), 32 girls had organic CPP. Pathological findings were detected in 33.3% (2 of 6) of girls aged 0-2 years, 15.6% (5 of 32) of girls aged 2-6 years, and 3.6% (8 of 219) of girls aged 6-8 years. Hypothalamic hamartoma and tumors in the pituitary stalk were the most common pathological findings. The likelihood of brain lesions decreased with age. Girls with organic CPP were more likely to be younger (6.1±2.4 vs. 7.3±1.3 years, p<0.01) than girls with idiopathic CPP. CONCLUSION: Older girls appeared to have a lower prevalence of organic CPP. Clinicians should cautiously use cranial MRI for girls aged 6-8 years with CPP.

Fish oil ameliorates neuropsychiatric behaviors and gut dysbiosis by elevating selected microbiota-derived metabolites and tissue tight junctions in rats under chronic sleep deprivation.

Neuropsychiatric behaviors caused by sleep deprivation (SD) are severe public health problems in modern society worldwide. This study investigated the effect of fish oil on neuropsychiatric behaviors, barrier injury, microbiota dysbiosis, and microbiota-derived metabolites in SD rats. The rats subjected to SD had significantly elevated blood levels of corticosteroid and lipopolysaccharides and exhibited anxiety-like behavior in the open field test, depression-like behavior in the forced swim test, and cognitive impairment in the Morris water maize test. We observed that the upregulation of proinflammatory cytokines in the SD rats resulted in colonic epithelial barrier injury including a decreased number of goblet cells and increased expression of selected tight junction proteins in the gut and brain. The gut microbiome status revealed a significant decrease in the microbial diversity in the SD rats, especially in probiotics. By contrast, a fish oil-based diet reversed SD-induced behavioral changes and improved the epithelial barrier injury and dysbiosis of the microbiota in the colon. These findings could be attributable to the increase in probiotics and short-chain fatty acid (SCFAs) production, improvement in selected intestinal barrier proteins, increase in SCFA receptor expression, and decrease in blood circulation proinflammatory status due to fish oil supplementation.

Development and Validation of Clinical Diagnostic Model for Girls with Central Precocious Puberty: Machine-learning Approaches.

BACKGROUND: A brief gonadotropin-releasing hormone analogues (GnRHa) stimulation test which solely focused on LH 30-minute post-stimulation was considered to identify girls with central precocious puberty (CPP). However, it was tested using traditional statistical methods. With advanced computer science, we aimed to develop a machine learning-based diagnostic model that processed baseline CPP-related variables and a brief GnRHa stimulation test for CPP diagnosis. METHODS: We recruited girls suspected of precocious puberty and underwent a GnRHa stimulation test at Children Hospital 2, Vietnam, and Cathay General Hospital, Taiwan. Clinical data, bone age measurement, and 30-min post-stimulation blood test were used to build up the predictive model. The candidate model was developed by different machine learning algorithms that were mainly evaluated by sensitivity, specificity, the area under the receiver operator characteristic curve (AUC), and F1-score in internal and external validation data to classify girls as CPP and non-CPP at different time-points (0-min, 30-min, 60-min, and 120-min post-stimulation). RESULTS: Among the 614 girls diagnosed with PP, 524 (85.3%) had CPP. The random forest algorithm yielded the highest value of F1-score (0.976), specificity (0.893), positive predicted value (0.987), and relatively high value of AUC (0.972) that contributed to high probability to identify CPP. The performance metrics of the 30-min post-stimulation diagnostic model including sensitivity and specificity surpassed those of the 0-minute model (0-min) and were equivalent to those of the model obtained 60-min and 120-min post-stimulation. Hence, our machine learning-based model helps shorten the stimulation test to 30 minutes after GnRHa injection, in general, it requires 120 minutes for a completed GnRHa stimulation test. CONCLUSIONS: We developed a diagnostic model based on clinical features and a single sample 30-minute post-stimulation to identify CPP in girls that can reduce distress for children caused by multiple blood samplings.

Fat-Free Mass and Skeletal Muscle Mass Gain Are Associated with Diabetes Remission after Laparoscopic Sleeve Gastrectomy in Males but Not in Females.

Besides massive body weight loss, laparoscopic sleeve gastrectomy (LSG) causes massive lean mass, including fat-free mass (FFM) and skeletal muscle mass (SM) that present higher metabolic rates in males. This study examines sex differences in FFM and SM changes of type 2 diabetes (T2D) remission at 12 months post-LSG. This cohort study recruited 119 patients (53.7% females) with T2D and obesity (body mass index 42.2 ± 7.0 kg/m2) who underwent LSG. Fat-mass (FM) loss was higher in males than in females (-12.8 ± 6.2% vs. -9.9 ± 5.0%, p = 0.02) after one-year post-operation. Regardless of the weight-loss difference, males had higher FFM and SM gain than did females (12.8 ± 8.0 vs. 9.9 ± 5.0% p = 0.02 and 6.5 ± 4.3% vs. 4.9 ± 6.2%, p = 0.03, respectively). Positive correlations of triglyceride reduction with FM loss (r = 0.47, p = 0.01) and SM gain (r = 0.44, p = 0.02) over 12 months post-operation were observed in males who achieved T2D remission. The T2D remission rate significantly increased 16% and 26% for each additional percentage of FFM and SM gain one year after LSG, which only happened in males. Increased FFM and SM were remarkably associated with T2D remission in males, but evidence lacks for females.

High-dose ferric citrate supplementation attenuates omega-3 polyunsaturated fatty acid biosynthesis via downregulating delta 5 and 6 desaturases in rats with high-fat diet-induced obesity.

Obesity is associated with an increased risk of an iron deficiency; however, a synergistic relationship between iron and lipid homeostasis was also observed. The aim of this study was to investigate the effects of pharmacological doses of iron supplementation on omega 3 (n-3) and omega 6 (n-6) polyunsaturated fatty acids (PUFAs). Sprague-Dawley (SD) rats were fed a normal diet or a 50% high-fat diet (HFD) without or with pharmacological doses of ferric citrate (0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks, and erythrocyte profiles of n-3 and n-6 PUFAs were quantitated. Ferric citrate supplementation showed dose-related effects on liver inflammation, liver iron accumulation, and increasing circulating levels of iron, erythrocyte degradation biomarkers LVV-hemorphin-7, malondialdehyde (MDA), and insulin. Obese rats supplemented with 2 g ferric iron per kg diet also had decreased levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and total n-3 PUFAs compared to rats fed a normal diet or HFD alone. A western blotting analysis revealed that iron-mediated downregulation of n-3 PUFA-converting enzymes (Δ5 and Δ6 desaturases) only occurred at high dosages (≥1 g ferric iron per kg diet). A Spearman correlation analysis showed that total liver iron and serum LVV-hemorphin-7 and MDA were negatively correlated with n-3 PUFAs and their converting enzymes (Δ5 and Δ6 desaturases) (all p < 0.05). In conclusion, obese rats that received high-dose ferric citrate supplementation (>1 g of ferric iron per kg diet) exhibited decreased n-3 PUFA levels via downregulation of expressions of Δ5 and Δ6 desaturase enzymes.