Search

Prodigiosin, a secondary metabolite produced by Serratia marcescens, has attracted attention due to its immunosuppressive, antimicrobial, and anticancer properties. However, information on the regulatory mechanism behind prodigiosin biosynthesis in S. marcescens remains limited. In this work, a prodigiosin-hyperproducing strain with the BVG90_22495 gene disrupted (ZK66) was selected from a collection of Tn5G transposon insertion mutants. Using real-time quantitative PCR (RT-qPCR) analysis, β-galactosidase assays, transcriptomics analysis, and electrophoretic mobility shift assays (EMSAs), the LysR-type regulator MetR encoded by the BVG90_22495 gene was found to affect prodigiosin synthesis, and this correlated with MetR directly binding to the promoter region of the prodigiosin-synthesis positive regulator PigP and hence negatively regulated the expression of the prodigiosin-associated pig operon. More analyses revealed that MetR regulated some other important cellular processes, including methionine biosynthesis, cell motility, H2O2 tolerance, heat tolerance, exopolysaccharide synthesis, and biofilm formation in S. marcescens. Although MetR protein is highly conserved in many bacteria, we report here on the LysR-type regulator MetR exhibiting novel roles in negatively regulating prodigiosin synthesis and positively regulating heat tolerance, exopolysaccharide synthesis, and biofilm formation. IMPORTANCE Serratia marcescens, a Gram-negative bacterium, is found in a wide range of ecological niches and can produce several secondary metabolites, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin shows diverse functions as an immunosuppressant, antimicrobial, and anticancer agent. However, the regulatory mechanisms behind prodigiosin synthesis in S. marcescens are not completely understood. Here, we adapted a transposon mutant library to identify the genes related to prodigiosin synthesis, and the BVG90_22495 gene encoding the LysR-type regulator MetR was found to negatively regulate prodigiosin synthesis. The molecular mechanism of the metR mutant hyperproducing prodigiosin was investigated. Additionally, we provided evidence supporting new roles for MetR in regulating methionine biosynthesis, cell motility, heat tolerance, H2O2 tolerance, and exopolysaccharide synthesis in S. marcescens. Collectively, this work provides novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers novel roles for the highly conserved MetR protein in regulating prodigiosin synthesis, heat tolerance, exopolysaccharide (EPS) synthesis, and biofilm formation. [ABSTRACT FROM AUTHOR]

Many hostile scenarios exist in real-life situations, where cooperation is disfavored and the collective behavior needs intervention for system efficiency improvement. Towards this end, the framework of soft control provides a powerful tool by introducing controllable agents called shills, who are allowed to follow well-designed updating rules for varying missions. Inspired by swarm intelligence emerging from flocks of birds, we explore here the dependence of the evolution of cooperation on soft control by an evolutionary iterated prisoner's dilemma (IPD) game staged on square lattices, where the shills adopt a particle swarm optimization (PSO) mechanism for strategy updating. We demonstrate that not only can cooperation be promoted by shills effectively seeking for potentially better strategies and spreading them to others, but also the frequency of cooperation could be arbitrarily controlled by choosing appropriate parameter settings. Moreover, we show that adding more shills does not contribute to further cooperation promotion, while assigning higher weights to the collective knowledge for strategy updating proves a efficient way to induce cooperative behavior. Our research provides insights into cooperation evolution in the presence of PSO-inspired shills and we hope it will be inspirational for future studies focusing on swarm intelligence based soft control. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to propose a new algorithm for pendulum-like oscillation control of an unmanned rotorcraft (UR) in a reconnaissance mission and improve the stabilizing performance of the UR's hover and stare. Design/methodology/approach – The algorithm is based on linear-quadratic regulator (LQR), of which the determinable parameters are optimized by the artificial bee colony (ABC) algorithm, a newly developed algorithm inspired by swarm intelligence and motivated by the intelligent behaviour of honey bees. Findings – The proposed algorithm is tested in a UR simulation environment and achieves stabilization of the pendulum oscillation in less than 4s. Research limitations/implications – The presented algorithm and design strategy can be extended for other types of complex control missions where relative parameters must be optimized to get a better control performance. Practical implications – The ABC optimized control system developed can be easily applied to practice and can safely stabilize the UR during hover and stare, which will considerably improve the stability of the UR and lead to better reconnaissance performance. Originality/value – This research presents a new algorithm to control the pendulum-like oscillation of URs, whose performance of hover and stare is a key issue when carrying out new challenging reconnaissance missions in urban warfare. Simulation results show that the presented algorithm performs better than traditional methods and the design process is simpler and easier. [ABSTRACT FROM AUTHOR]

With the construction and development of nuclear facilities, many nuclear production sites need to monitor artificial radioactive aerosol. However, radon and its daughters are ubiquitous in the environment, and their concentration levels are considerably higher than those of artificial radioactive aerosols. Therefore, artificial radioactive aerosol monitors can reliably measure environmental artificial radioactive aerosol only by testing the effectiveness of radon daughter compensation. By studying the mechanism of radon progeny aerosol and establishing a radon progeny aerosol control device that meets the measurement standards, the concentration of radon progeny aerosol in a radioactive aerosol monitor in certain places can be corrected. Thus, the interference to the measurement of specific radioactive aerosol can be reduced in the high radon environment of such places. In this study, we established a radon progeny aerosol control device that can be used to compensate the radon daughter aerosol for the radioactive aerosol monitoring equipment and help to eliminate or reduce the radon progeny aerosol interference of the radon daughter aerosol correction radioactive aerosol monitoring equipment. [ABSTRACT FROM AUTHOR]

Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion: These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a-5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression. [ABSTRACT FROM AUTHOR]

The present study was aimed at investigating the efficacy and mechanism(s) of action of a Chinese herbal formulation, Liuwei Dihuang (LWDH), as a prospective natural weight-lowering product. Following a 2-week acclimation period, 48 obesity-prone (OP-CD) rats were divided into 4 groups (n = 12 each). One group served as a positive control for obesity (OP), while the other 3 were challenged twice daily by oral gavage with total daily dosages of 500, 1500, or 3500 mg/kg BW LWDH, respectively, for 10 weeks. One group (n = 12) of obesity-resistant (OR-CD) rats served as the normal control group. All rats were fed the same AIN-93G dietmodified to contain 60% energy from fat. The highest LWDH dose significantly reduced body weight during the last 4 weeks of treatment. Food intake was reduced beginning in week 2. The high LWDH dose lowered serum triglyceride (TG) and nonesterified fatty acid (NEFA) levels and body fat. Both the high and medium doses also lowered serum leptin and insulin levels. Liver function testing revealed no adverse side effects under the current experimental conditions. The results of the present study suggest that LWDH has potential as a preventive or therapeutic natural product against overweight and obesity. [ABSTRACT FROM AUTHOR]

Prodigiosin (PG), a red linear tripyrrole pigment normally secreted by Serratia marcescens, has received attention for its reported immunosuppressive, antimicrobial, and anticancer properties. Although several genes have been shown to be important for prodigiosin synthesis, information on the regulatory mechanisms behind this cellular process remains limited. In this work, we identified that the transcriptional regulator RcsB encoding gene BVG90_13250 (rcsB) negatively controlled prodigiosin biosynthesis in S. marcescens. Disruption of rcsB conferred a remarkably increased production of prodigiosin. This phenotype corresponded to negative control of transcription of the prodigiosin-associated pig operon by RcsB, probably by binding to the promoter region of the prodigiosin synthesis positive regulator FlhDC. Moreover, using transcriptomics and further experiments, we revealed that RcsB also controlled some other important cellular processes, including swimming and swarming motilities, capsular polysaccharide production, biofilm formation, and acid resistance (AR), in S. marcescens. Collectively, this work proposes that RcsB is a prodigiosin synthesis repressor in S. marcescens and provides insight into the regulatory mechanism of RcsB in cell motility, capsular polysaccharide production, and acid resistance in S. marcescens. [ABSTRACT FROM AUTHOR]

Background: We previously identified the urinary biomarkers to diagnose calcium deficiency and nutritional rickets by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS). To find biomarkers of calcium deficiency and further confirm these biomarkers in serum, we performed serum metabolomics analysis of calcium-deficient rats. Methods: A calcium-deficient rat model was established with a low-calcium diet for 12 weeks. Serum metabolomics based UPLC/Q-TOF MS/MS and multivariate statistical analysis was performed to identify the alterations in metabolites associated with calcium deficiency in rats. Results: Bone mineral density, serum parathyroid hormone and alkaline phosphatase were significantly decreased in the low-calcium diet group (LCG) compared to the normal calcium diet group (NCG). Serum metabolic-profiling analysis could definitively distinguish between the LCG and NCG and identified 24 calcium-deficient biomarkers. Three metabolites (indoxyl sulfate, phosphate, and taurine) of the 24 biomarkers were found in our previous urinary metabolomics study of rats with a calcium deficiency and nutritional rickets. The areas under the curve (AUCs) of these three biomarkers were greater than 0.8, and the combination of any two biomarkers was higher than 0.95. Conclusion: Dietary calcium deficiency induced the alterations of metabolites in the serum of rats, and the three identified biomarkers had relatively high diagnostic values for calcium deficiency in rats. [ABSTRACT FROM AUTHOR]

Chronic exposure of pancreatic β-cells to saturated fatty acid (palmitic or stearic acid) is a leading cause of impaired insulin secretion. However, the molecular mechanisms underlying stearic-acid-induced β-cell dysfunction remain poorly understood. Emerging evidence indicates that miRNAs are involved in various biological functions. The aim of this study was to explore the differential expression of miRNAs and mRNAs, specifically in stearic-acid-treated- relative to palmitic-acid-treated β-cells, and to establish their co-expression networks. β-TC-6 cells were treated with stearic acid, palmitic acid or normal medium for 24 h. Differentially expressed miRNAs and mRNAs were identified by high-throughput sequencing and bioinformatic analysis. Co-expression network, gene ontology (GO) and pathway analyses were then conducted. Changes in the expression of selected miRNAs and mRNAs were verified in β-TC-6 cells and mouse islets. Sequencing analysis detected 656 known and 1729 novel miRNAs. miRNA-mRNA network and Venndiagram analysis yielded two differentially expressed miRNAs and 63 mRNAs exclusively in the stearic-acid group. miR-374c-5p was up-regulated by a 1.801 log2(fold-change) and miR-297b-5p was down-regulated by a -4.669 log2(fold-change). We found that miR- 297b-5p and miR-374c-5p were involved in stearic-acid-induced lipotoxicity to β-TC-6 cells. Moreover, the effects of miR-297b-5p and miR-374c-5p on the alterations of candidate mRNAs expressions were verified. This study indicates that expression changes of specific miRNAs and mRNAs may contribute to stearic-acid-induced β-cell dysfunction, which provides a preliminary basis for further functional and molecular mechanism studies of stearic-acid-induced β-cell dysfunction in the development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Chronic exposure to high concentrations of stearic acid (C18:0) can result in β-cell dysfunction, leading to development of type 2 diabetes. However, the molecular mechanisms underlying the destructive effects of stearic acid on β-cells remain largely unknown. In this study, we aimed to investigate the role of miR-297b-5p on stearic acid-induced β-cell apoptosis. Differential expression of microRNAs (miRNAs) was assessed in a β-TC6 cell line exposed to stearic acid, palmitic acid, or a normal culture medium by high-throughput sequencing. The apoptosis rate was measured by flow cytometry after miR-297b-5p mimic/inhibitor transfection, and large-tumor suppressor kinase 2 (LATS2) was identified as a target of miR-297b-5p using a luciferase activity assay. In vivo, C57BL/6 mice were fed with normal and high-stearic-acid diet, respectively. Mouse islets were used for similar identification of miR-297b-5p and Lats2 in β-TC6 cell. We selected two differentially expressed miRNAs in stearic acid compared with those in the palmitic acid and control groups. miR-297b-5p expression was significantly lower in β-TC6 cells and mouse islets in stearic acid than in control group. Upregulation of miR-297b-5p alleviated the stearic acid-induced cell apoptosis and reduction in insulin secretion by inhibiting Lats2 expression in vitro. Meanwhile, silencing Lats2 significantly reversed the stearic acid-stimulated β-cell dysfunction in both β-TC6 cells and islets. Our findings indicate a suppressive role for miR-297b-5p in stearic acid-induced β-cell apoptosis, which may reveal a potential target for the treatment of β-cell dysfunction in the pathogenesis of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate whether xanthine oxidase (XO), a key enzyme in uric acid (UA) metabolism and a major source of reactive oxygen species, plays a causal and important role in the development of type 2 diabetes mellitus (T2DM) in a large prospective cohort study.Research Design and Methods: A total of 4,412 diabetes-free adults (2,071 women and 2,341 men) aged 30-65 years at baseline in 2008 were involved. Participants were followed for incident change of glucose metabolism during an average of 4.7 years. At baseline, serum XO and UA, serum lipids, and glucose homeostasis indexes including fasting blood glucose (FBG), 2-h blood glucose (PBG), glycosylated hemoglobin A1c (HbA1c), and fasting insulin were tested for analysis.Results: During an average follow-up period of 4.7 years, 249 women and 360 men developed new-onset T2DM. Serum XO activity was positively associated with UA concentration (all P values <0.001). When XO activity and UA concentration were considered in the same model of the sex-specific analysis, only XO activity was significantly associated with the incidence of T2DM, with the hazard ratios from the bottom to the top quartile of XO activity being 1.00, 1.67 (95% CI 1.00-2.79), 1.86 (1.11-3.13), and 2.36 (1.43-3.90) in women and 1.00, 1.01 (0.68-1.52), 1.41 (0.98-2.03), and 1.90 (1.30-2.78) in men.Conclusions: Elevated serum XO activity, but not UA concentration, was associated with an increased risk of developing T2DM in women and men with mutual adjustment for XO and UA. Further studies are needed to examine the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background/Aims: Atherosclerosis is a multifactorial chronic disease and is the main cause of death and impairment in the world. Endothelial injury and apoptosis play a crucial role in the onset and development of atherosclerosis. MicroRNAs (miRNAs) have been proven to be involved in the pathogenesis of atherosclerosis. However, studies of the functional role of apoptosis-related miRNAs in the endothelium during atherogenesis are limited. Methods: Cell injury and apoptosis were measured in five types of cells transfected with miR-1185 or co-transfected with miR-1185 and its inhibitor. Bioinformatics analysis and a luciferase reporter assay were used to confirm the targets of miR-1185. The effects of the targets of miR-1185 on endothelial apoptosis were determined using small-interfering RNA. Results: In this study, we first report that miR-1185 significantly promoted apoptosis in endothelial cells but not in vascular smooth muscle cells and macrophages. A mechanistic analysis showed that ultraviolet irradiation resistance-associated gene (UVRAG) and krev1 interaction trapped gene 1 (KRIT1), targets of miR-1185, mediated miR-1185-induced endothelial cell apoptosis. Conclusion: The results revealed the impact of miR-1185 on endothelial apoptosis, suggesting that miR-1185 may be a potential target for the prevention and treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

AIMS: The aims were to investigate the serum free fatty acid (FFA) and esterified fatty acid (EFA) profiles and to identify biomarkers that can be used to identify patients with epithelial ovarian cancer (EOC) based on the metabolomics approach. METHODS: We applied a targeted gas chromatography-mass spectrometry metabolomics approach to serum samples from 40 EOC patients and 35 healthy controls for achieving the FFA and EFA profiles. These metabolite profiles were processed using multivariate analysis to obtain potential biomarkers. And then, some independent samples were chosen to validate these potential biomarkers. RESULTS: There were higher saturated fatty acids and lower unsaturated fatty acids in EOC patients when compared with the healthy controls. EFA (C16:0), EFA (C18:0) and FFA (C16:0) were identified as potential biomarkers that distinguished EOC from the healthy controls. The areas under the curve from the EFA (C16:0), EFA (C18:0) and FFA (C16:0) in validated study were 0.745, 0.701, 0.682, respectively. CONCLUSION: Our study provides useful information to bridge the gaps in our understanding to the fatty acids metabolic alterations associated with EOC, and this study has demonstrated saturated fatty acid biomarkers might be helpful for the detection and characterization of EOC patients. [ABSTRACT FROM AUTHOR]

Background: Results of longitudinal researches regarding the temporal relationship between dyslipidemia and insulin resistance (IR) are inconsistent. This study assessed temporal relationships of blood lipids with IR and determined whether there are any mediating effects existed in these temporal relationships. Methods: This study examined a longitudinal cohort of 3325 subjects aged 20-74 years from China with an average of 4.2 years follow-up. Measurements of fasting blood lipids, as well as fasting and 2-h serum glucose and insulin, were obtained at two time points. The Gutt index and HOMA-IR were calculated as indicators of peripheral IR and hepatic IR. A cross-lagged path analysis was performed to examine the temporal relationships between blood lipids and IR. A mediation analysis was used to examine mediating effect. Results: After adjusting for covariates, the cross-lagged path coefficients from baseline TG and HDL-C to follow-up Gutt index were significantly greater than those from baseline Gutt index to follow-up TG and HDL-C (β1 = -0.131 vs β2 = -0.047, P < 0.001 for TG; β1 = 0.134 vs β2 = 0.023, P < 0.001 for HDL-C). The path coefficients from baseline TG and HDL-C to follow-up 2-h insulin were significantly greater than those from baseline 2-h insulin to follow-up TG and HDL-C (β1 = 0.125 vs β2 = 0.040, P < 0.001 for TG; β1 = -0.112 vs β2 = -0.026, P < 0.001 for HDL-C). 2-h insulin partially mediated the effect of TG/HDL-C on Gutt index with a 59.3% mediating effect for TG and 61.0% for HDL-C. Conclusions: These findings provide strong evidence that dyslipidemia probably precede peripheral IR and that 2-h insulin partially mediates this unidirectional temporal relationship. [ABSTRACT FROM AUTHOR]

Background: Early detection and diagnosis are very important for autism. Current diagnosis of autism relies mainly on some observational questionnaires and interview tools that may involve a great variability. We performed a metabolomics analysis of serum to identify potential biomarkers for the early diagnosis and clinical evaluation of autism. Methods: We analyzed a discovery cohort of patients with autism and participants without autism in the Chinese Han population using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS) to detect metabolic changes in serum associated with autism. The potential metabolite candidates for biomarkers were individually validated in an additional independent cohort of cases and controls. We built a multiple logistic regression model to evaluate the validated biomarkers. Results: We included 73 patients and 63 controls in the discovery cohort and 100 cases and 100 controls in the validation cohort. Metabolomic analysis of serum in the discovery stage identified 17 metabolites, 11 of which were validated in an independent cohort. A multiple logistic regression model built on the 11 validated metabolites fit well in both cohorts. The model consistently showed that autism was associated with 2 particular metabolites: sphingosine 1-phosphate and docosahexaenoic acid. Limitations: While autism is diagnosed predominantly in boys, we were unable to perform the analysis by sex owing to difficulty recruiting enough female patients. Other limitations include the need to perform test-retest assessment within the same individual and the relatively small sample size. Conclusion: Two metabolites have potential as biomarkers for the clinical diagnosis and evaluation of autism. [ABSTRACT FROM AUTHOR]

Background Acute lymphoblastic leukemia (ALL) is a common hematological malignant neoplasm that typically affects children. Although intense chemotherapeutic regimens have been useful to combat the disease, approximately 20% of patients will relapse despite treatment. Diagnosing ALL requires bone marrow puncture procedure, which many parents do not consent to for it is invasive. Additionally, metabolic alterations associated with the disease are unclear. Methods Metabolic alterations associated with ALL were investigated by performing serum metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Ingenuity Pathways Analysis (IPA) was also performed. Results Thirty metabolites (17 detected in positive mode and 13 in negative mode) were differentially expressed between patients with ALL and control patients; these metabolites were selected as potential biomarkers. Based on IPA analysis, glycerophospholipid metabolism is deregulated in patients with ALL and may represent an underlying metabolic pathway associated with disease progression. Conclusions Metabolomics can be used to analyze the metabolic activity of ALL patients compared to healthy controls. The data we provide here suggest that glycerophospholipid metabolism may be a key mechanism underlying disease progression and development. [ABSTRACT FROM AUTHOR]

Although both SLC30A8 rs13266634 single nucleotide polymorphism and plasma zinc concentrations have been associated with impaired glucose regulation (IGR) and type 2 diabetes (T2D), their interactions for IGR and T2D remain unclear. Therefore, to assess zinc-SLC30A8 interactions, we performed a case-control study in 1,796 participants: 218 newly diagnosed IGR patients, 785 newly diagnosed T2D patients, and 793 individuals with normal glucose tolerance. After adjustment for age, sex, BMI, family history of diabetes, and hypertension, the multivariable odds ratio (OR) of T2D associated with a 10 µg/dL higher plasma zinc level was 0.87 (95% CI 0.85-0.90). Meanwhile, the OR of SLC30A8 rs13266634 homozygous genotypes CC compared with TT was 1.53 (1.11-2.09) for T2D. Similar associations were found in IGR and IGR&T2D groups. Each 10 µg/dL increment of plasma zinc was associated with 22% (OR 0.78 [0.72-0.85]) lower odds of T2D in TT genotype carriers, 17% (0.83 [0.80-0.87]) lower odds in CT genotype carriers, and 7% (0.93 [0.90-0.97]) lower odds in CC genotype carriers (P for interaction = 0.01). Our study suggested that the C allele of rs13266634 was associated with higher odds of T2D, and higher plasma zinc was associated with lower odds. The inverse association of plasma zinc concentrations with T2D was modified by SLC30A8 rs13266634. Further studies are warranted to confirm our findings and clarify the mechanisms underlying the interaction between plasma zinc and the SLC30A8 gene in relation to T2D. [ABSTRACT FROM AUTHOR]

Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid supplement, HFolS) mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS) were more vulnerable to suffer from obesity (p = 0.009), glucose intolerance (p < 0.001) and insulin resistance (p < 0.001), compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring. [ABSTRACT FROM AUTHOR]

Background: Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods: The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results: Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and nondeficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a lowcalcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calciumdeficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson correlation, r = 0.53, P = 0.0001) and citrate (Pearson correlation, r = -0.43, P = 0.001), were further confirmed in 70 women. Conclusions: To our knowledge, this is the first report of reliable biomarkers of calcium deficiency, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of calcium deficiency. The correlations between calcium intake and two of the biomarkers provide a rationale or potential for further assessment and elucidation of the metabolic responses of calcium deficiency in humans. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein lipase (LPL) and serum 25-hydroxyvitamin D [25(OH)D] play important roles in the regulation of lipid metabolism. Although dyslipidemia is associated with insulin resistance (IR) and type 2 diabetes (T2D), there are limited data available regarding the relationship of LPL and 25(OH)D to IR and T2D at a population level. The objective of the present study is to investigate the associations of LPL and 25(OH)D with IR and T2D in a Chinese population. Methods: The study cohort consisted of 2708 subjects (1326 males, 1382 females; mean age 48.5 ± 12.6 years) in main communities of Harbin, China. Serum 25(OH)D, LPL, free fatty acids (FFAs), fasting glucose (FG), fasting insulin, lipid profile, apoA and apoB concentrations were measured. Results: Serum 25(OH)D concentration was positively associated with LPL (β = 0.168, P < 0.001). LPL was inversely associated with IR and T2D. Subjects in the lowest quartile of LPL had the highest risk of IR [odds ratio (OR) = 1.85, 95% CI = 1.22-2.68] and T2D (OR = 1.65, 95% CI = 1.14-2.38). Serum 25(OH)D was also inversely associated with IR and T2D. Vitamin D deficiency [25(OH)D < 20 ng/ml] was associated with an increasing risk of IR (OR = 1.91, 95% CI = 1.23-2.76) and T2D (OR = 2.06, 95% CI = 1.37-3.24). The associations of 25(OH)D with IR and T2D were attenuated by further adjustment for LPL. Conclusions: LPL is associated with serum 25(OH)D, IR and T2D in the Chinese population. These results suggest a potential mediating role of LPL in the associations of 25(OH)D with IR and T2D [ABSTRACT FROM AUTHOR]

Elevated serum free fatty acids (FFAs) levels play an important role in the development of insulin resistance (IR) and diabetes. We investigated the dynamic changes and the underlying regulatory mechanism of postprandial FFA profile in hyperlipidemia (HLP) and their relation with insulin sensitivity in both humans and mice. We found that serum stearic acid (SA) is the only fatty acid that is increased dramatically in the postprandial state. The elevation of SA is due to increased insulin-stimulated de novo synthesis mediated by sterol regulatory element--binding protein-1c (SREBP-1c)/acetyl-CoA carboxylase/fatty acid synthase/elongation of long-chain fatty acid family member 6 (ELOVL6) and the elongation of palmitic acid (PA) catalyzed by ELOVL6. Downregulation of SREBP-1c or ELOVL6 by small interfering RNA can reduce SA synthesis in liver and serum SA level, followed by amelioration of IR in HLP mice. However, inhibition of SREBP-1c is more effective in improving IR than suppression of ELOVL6, which resulted in accumulation of PA. In summary, increased postprandial SA is caused by the insulin-stimulated SREBP-1c pathway and elongation of PA in HLP. Reduction of postprandial SA is a good candidate for improving IR, and SREBP-1c is potentially a better target to prevent IR and diabetes by decreasing SA. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which focuses on the meta-analyses of TNF-alpha-238, -308, single nucleotide polymorphisms that have no significant association with type 2 diabetes but are associated with type 1 diabetes mellitus and metabolic syndrome.

Despite the availability of vaccines, influenza is a considerable public health problem, which emphasizes the need for development of additional strategies to enhance host defense against influenza. Wolfberry, or goji berry, long used as a medicinal food in China, has recently been shown to improve immune response in mice. Because immune response plays a key role in the body's defense against pathogens, we hypothesized that wolfberry may increase host resistance to influenza infection by enhancing immune response. To test this hypothesis, we fed adult mice (4 mo old) a milk-based preparation of wolfberry called Lacto-Wolfberry (LWB) for 4 wk and then infected them with influenza A/Puerto Rico/8/34 (HIND while continuing the same experimental diets. Viral titer, lung pathology, and immune response were determined at different time points postinfection. LWB supplementation prevented infection-induced weight loss and reduced lung pathology on days 6 and 9 postinfection (P < 0.05). LWB-fed mice showed overall, significantly higher concanavalin A-induced IL-2 production (P< 0.05). Furthermore, we found positive correlations between weight loss and lung viral titer, pathology score, TNFa, and IL-6 production as well as negative correlations with Tcell proliferation and IL-2 production (all Ps 0.05). These results indicate that LWB supplementation can attenuate symptoms and pathology of influenza infection by decreasing inflammatory cytokines in lungs while enhancing systemic T cell-mediated function as measured by their ability to produce IL-2. [ABSTRACT FROM AUTHOR]

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism. [ABSTRACT FROM AUTHOR]

Objective: We assessed whether dietary calcium intake or calcium supplements associated with body composition and obesity in a Chinese population. Methods: A cross-sectional survey was performed in a population of 8940, aged 20 to 74 y. 8127 participants responded (90.9%). Height, weight, fat mass (FM), waist circumference (WC) and hip circumference were measured. Obesity definition: body mass index (BMI) ⩾28 kg/m2 (overall obesity); WC ⩾85 cm for men or ⩾80 cm for women (abdominal obesity I) and waist hip ratio (WHR) $0.90 for men or $0.85 for women (abdominal obesity II). The data on dietary calcium and calcium supplements were collected using food-frequency questionnaire and self-report questionnaire. Multivariate linear and multivariable logistic regressions were used to examine the associations between dietary calcium intake or calcium supplements and body composition and obesity. Principal Findings: The average dietary calcium intake of all subjects was 430 mg/d. After adjusting for potential confounding factors, among women only, negative associations were observed between habitual dietary calcium intake and four measures of body composition (β, -0.086, P<0.001 for BMI; β, -0.072, P<0.001 for WC; β, -0.044, P<0.05 for WHR; and β, -0.058, P<0.01 for FM, respectively) and both measures of abdominal obesity (Odds Ratio [OR] = 0.86, 95% Confidence Interval [CI], 0.80-0.93; P<0.001, for abdominal obesity I; OR = 0.92, 95% CI, 0.86-0.99; P = 0.026, for abdominal obesity II). These associations were not observed among men (P>0.05). Similarly, among both men and women, we did not observe significant associations between calcium supplements and any measures of body composition or abdominal obesity (P>0.05). Conclusions: Dietary calcium from food rather than elemental calcium from calcium supplements has beneficial effects on the maintenance of body composition and preventing abdominal obesity in Chinese women. [ABSTRACT FROM AUTHOR]

The aim of this meta-analysis was to determine the nature of the association between TNF 238 G/A polymorphism and the risk for T2D. We searched databases updated on January 2009 for all publications on the association between this variation and T2D. Data on genotypes and the numbers of cases and controls were assessed using Review Manager 4.2. Meta-analysis of the overall and specific populations was conducted, and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the fixed-effect model. I2 statistic was calculated to examine heterogeneity, and publication bias was evaluated by Egger test. The overall OR (95% CI) for AA and GA genotypes versus GG genotype for TNF-α-238 was 1.15 (0.92–1.44), which in European and Asian populations were 1.18 (0.92–1.51) and 1.13 (0.62–2.04), respectively. This first meta-analysis of data from the current and published studies did not detect any association between the polymorphism of TNF 238 G/A and risk for T2D. [ABSTRACT FROM AUTHOR]