Bee Bread Ameliorates Vascular Inflammation and Impaired Vasorelaxation in Obesity-Induced Vascular Damage Rat Model: The Role of eNOS/NO/cGMP-Signaling Pathway

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role.     

Metabolic Profiling of VOCs Emitted by Bacteria Isolated from Pressure Ulcers and Treated with Different Concentrations of Bio-AgNPs

Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL⁻¹. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled.     

Relationship of cow and calf circulating lipidomes with colostrum lipid composition and metabolic status of the cow

Newborn calves rely on lipids in colostrum for energy and immune function. The lipid concentration in colostrum, however, is highly variable, and little is known about its composition and maternal factors that influence its composition. The first objective was to measure plasma lipid composition of multiparous cows at 35 d before calving (BC; 35 ± 3 d; ± standard deviation) and 7 d BC (7 ± 2 d), their colostrum, and serum lipid composition of calves (24 h after birth) using multiple reaction monitoring profiling, which is an exploratory and highly sensitive lipidomic analysis method that screens lipids based on chemical functionality. Second, data were analyzed to determine if there were relationships between circulating lipids in the cow, colostrum lipids, and calf serum lipids. Third, relationships between markers of metabolic status of the cows and circulating and colostrum lipids were analyzed with correlation analysis. Blood was sampled and plasma prepared from multiparous cows (n = 16) at 35 and 7 d BC. Within 3 h of parturition, colostrum was collected from cows and fed to her calf. Calves received another feeding of colostrum within 12 h after birth and a serum sample was collected from each calf 24 h after the first feeding of colostrum. The metabolic status of cows was evaluated using insulin, glucose, and nonesterified fatty acid area under the curve in response to an intravenous glucose tolerance test performed at 3 wk BC. Lipids were extracted from plasma, colostrum, and calf serum and were analyzed using multiple reaction monitoring profiling. Concentration of lipids were calculated using spiked in standards and expressed as percent of lipids identified. Data were uploaded into MetaboAnalyst 5.0 for multivariate and univariate analysis. Principal component analysis indicated that circulating lipids in the cow and calf were distinct from lipids in colostrum. Phosphatidylglycerol (PG) concentration was greater in colostrum and calf serum than in cow plasma, with 23 of the 24 PG found in colostrum also found in calf serum. In response to intravenous glucose tolerance test in late gestation, nonesterified fatty acid area under the curve was positively related to total triacylglycerols lipids in 7 d BC plasma (r = 0.63) but negatively related to total membrane lipids in colostrum (r = ?0.55). Thus, the metabolic status of the dam influences circulating lipids and colostrum lipid content. Moreover, the circulating lipidome of the cow and calf are similar to one another and distinct from the colostrum lipidome, except for PG, where it appears that colostrum serves as the source for PG in the calf's circulation.     

High-Fat Diet Aggravates Cerebral Infarct,Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model

Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.     

电喷雾质谱法示踪钨回收过程离子的转化路径

将环隙式离心萃取器(ACCs)与电喷雾飞行时间质谱(ESI-TOF-MS)相结合，在线监测了回收过程中的钨萃取行为(宏观)和钨形态的转化路径(微观)，发现宏观萃取反应和微观离子形态转化同时发生并相互补充。伯胺N1923萃取钨在144 s内即可达到萃取平衡，萃取率高达98%以上，同时，酸钨比n(H)/n(W)是一个关键变量，当酸钨比n(H)/n(W)=2.4时，全流程钨回收率超过93%。最后，得到了基于钨形态监测的萃取机理，同时，减少原料液中W1含量，增加W10含量，可有效提高钨回收效率。     

Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

TiO2/MXene-Assisted LDI-MS for Urine Metabolic Profiling in Urinary Disease

Cancer remains an intractable medical problem. Rapid diagnosis and identification of cancer are critical to differentiate it from nonmalignant diseases. High-throughput biofluid metabolic analysis has potential for cancer diagnosis. Nevertheless, the present metabolite analysis method does not meet the demand for high-throughput screening of diseases. Herein, a high-throughput, cost-effective, and noninvasive urine metabolic profiling method based on TiO₂/MXene-assisted laser desorption/ionization mass spectrometry (LDI-MS) is presented for the efficient screening of bladder cancer (BC) and nonmalignant urinary disease. Combined with machine learning, TiO₂/MXene-assisted LDI-MS enables high diagnostic accuracy (96.8%) for the classification of patient groups (including 47 BC and 46 ureteral calculus (UC) patients) from healthy controls (113 cases). In addition, BC patients can also be identified from noncancerous UC individuals with an accuracy of 88.3% in the independent test cohort. Furthermore, metabolite variations between BC and UC individuals are investigated based on relative quantification, and related pathways are also discussed. These results suggest that this method, based on urine metabolic patterns, provides a potential tool for rapidly distinguishing urinary diseases and it may pave the way for precision medicine.     

Bioactive compounds and antioxidant activities of the Korean lotus leaf (Nelumbo nucifera) condiment: volatile and nonvolatile metabolite profiling during fermentation

Recent studies have shown that lotus (Nelumbo nucifera) leaf has various pharmacological effects. However, there have been no scientific investigations into these leaves as a fermented crude liquid. This study compared the in vitro antioxidant capacity of lotus leaf‐fermented broth (LLFB) with that of 57° Brix sugar broth (SB) as a control over a period of 6 months based on 1,1‐diphenyl‐2‐picrylhydrazyl radical scavenging activity, ferric ion reducing power, superoxide dismutase‐like activity, tyrosinase inhibition and nitrite scavenging activity. The dominant species during fermentation process were Leuconostoc lactis and Saccharomyces cerevisiae for LLFB. A total of thirty‐six metabolites such as alkaloids, fatty acids, organic acids, phenolics, sugar and sugar derivatives, ethyl esters and monoterpenoids differed between SB and LLFB using gas chromatography–mass spectrometry. Meanwhile, nine volatile compounds in LLFB contributed pleasant, slightly sweetish and fruity odour of condiment and sensory evaluation score of 4.06 ± 1.52 in the proportion of 1:9 LLFB/water.     

The effect of optimized carbon source on the synthesis and composition of exopolysaccharides produced by Lactobacillus paracasei

This study aimed to predict the optimal carbon source for higher production of exopolysaccharides (EPS) by Lactobacillus paracasei TD 062, and to evaluate the effect of this carbon source on the production and monosaccharide composition of EPS. We evaluated the EPS production capacity of 20 strains of L. paracasei under the same conditions. We further investigated L. paracasei TD 062, which showed the highest EPS-producing activity (0.609 g/L), by examining the associated biosynthesis pathways for EPS. Genomics revealed that fructose, mannose, trehalose, glucose, galactose, and lactose were carbon sources that L. paracasei TD 062 could use to produce EPS. We identified an EPS synthesis gene cluster that could participate in transport, export, and sugar chain synthesis, and generate 6 sugar nucleotides. Experimental results showed that the sugar content of the EPS produced using fermentation with the optimized carbon source (fructose, mannose, trehalose, glucose, galactose, and lactose) increased by 115%. Furthermore, use of the optimized carbon source changed the monosaccharide content of the associated EPS. The results of enzyme activity measurements showed significant increases in the activity of 2 key enzymes involved in the glycoside synthesis pathway. Our study revealed that optimizing the carbon source provided for fermentation not only increased the production of EPS, but also affected the composition of the monosaccharides by increasing enzyme activity in the underlying synthesis pathways, suggesting an important role for carbon source in the production of EPS by L. paracasei TD 062.