Prostaglandin B1 Research Articles

Dietary high plant protein and high lipid impaired the intestine health of grouper by disrupting oxidative stress, immune response, and protein metabolism

This study aimed to investigate the molecular mechanisms underlying the detrimental effects of high lipid (HL) and high plant-protein (HP) diets on gut health in pearl gentian grouper, Epinephelus fuscoguttatus♂ × Epinephelus lanceolatus♀. Thus, grouper were randomly distributed into 12 plastic tanks, which were randomly assigned to four diet groups: control (C, 9.48 % lipid, 46.21 % protein), high lipid (HL, 16.70 % lipid, 46.37 % protein), high plant-protein (HP, 9.38 % lipid, 46.50 % protein), high lipid and high plant-protein (HLP, 16.67 % lipid, 46.54 % protein). After an 8-week feeding trial, the HL and HP treatments led to impaired growth performance, compromised gut structure, suppressed immune components, reduced antioxidant defense through the Keap/Nrf2 signaling, and inhibited protein metabolism via the PI3K/AKT/mTOR signaling. Notably, their combined effects (HLP) further exacerbated it. A significant decrease in the proportion of unclassified_Peptostreptococcaceae, Clostridium, and Curvibacter in all treatment groups. The Streptococcus, Lactobacillus, and Bosea were influenced by the interaction between dietary lipids and plant proteins. 14 metabolites that exhibited significant differences among all treatment groups, including arginine, prostaglandin B1, cortexolone, alpha-linolenic acid, and allocholic acid. The HL treatment primarily affected pathways related to lipid metabolism and immunomodulation, while the HP treatment predominantly influenced pathways associated with protein metabolism and immunomodulation. Our findings also indicated that the HP factor played a more prominent role in shaping the metabolic response of fish to the HLP intervention. Furthermore, a significant positive correlation between the Clostridium and the metabolites Cortexolone and Allocholic acid, while a negative correlation was observed between the Streptococcus, Lactobacillus, and Lactococcus and these metabolites. In conclusion, our study demonstrates that excessive inclusion of plant proteins and/or lipids negatively affects gut health in grouper by disrupting oxidative stress, immune response, and protein metabolism through modulation of the gut microbial-metabolite crosstalk.

Persistent exposure to artificial light at night (ALAN) accelerates metamorphosis and colonization in larvae of marine shellfish

The ongoing course of urbanization has led to excessive use of artificial light at night (ALAN), which has rapidly become an important source of pollution in many cities. The Pacific abalone (Haliotis discus hannai) Larvae were kept under a 12/12 h light/dark photoperiod (DD) in order to determine the effects of ALAN on embryonic development. To simulate the street lighting conditions at night, the artificial light was switched on from 18:00 until midnight (AD) or until 06:00 the next day (ND). Moreover, Groups AD and ND had a considerably greater hatching success rate and metamorphosis rate than Group DD (P < 0.05), whereas Group DD had a significantly longer hatching period and course to complete the metamorphosis of the larvae (P < 0.05). Transcriptomic analyses showed that members of Groups AD and DD had considerably higher expression levels of genes involved in ribosome biogenesis, spliceosome function, and the mRNA surveillance pathway. Prostaglandin B2, L-palmitoylcarnitine, stearic acid, palmitic acid, leukotriene C4, and arachidonic acid were screened by non-targeted metabolomics as differential metabolic markers that played a vital role in the response of larvae to different ALAN conditions. Multi-omics correlation analysis suggested that five pathways related to fatty acid synthesis, catabolism, and metabolism, such as biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, were enriched in each comparison. Further quantitative analysis showed that compared to Group DD, 33 out of 50 fatty acids were upregulated in Group AD, and the levels of almost all fatty acids were increased in Group ND, which in turn suggested that fatty acids played a vital role in the physiological response of larvae to illumination changes. The findings of this work were significant for the unbiased and full-scale assessment of the ecological effects of ALAN, as well as the structural stability of the marine benthic community.

Multi-omics analysis of functional substances and expression verification in cashmere fineness.

Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis. This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques. The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis. This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.

Plasma metabolomic profiling of patients with transient ischemic attack reveals positive role of neutrophils in ischemic tolerance

Transient ischemic attack (TIA) induces ischemic tolerance that can reduce the subsequent ischemic damage and improve prognosis of patients with stroke. However, the underlying mechanisms remain elusive. Recent advances in plasma metabolomics analysis have made it a powerful tool to investigate human pathophysiological phenotypes and mechanisms of diseases. In this study, we aimed to identify the bioactive metabolites from the plasma of patients with TIA for determination of their prophylactic and therapeutic effects on protection against cerebral ischemic stroke, and the mechanism of TIA-induced ischemic tolerance against subsequent stroke. Metabolomic profiling using liquid chromatography-mass spectrometry was performed to identify the TIA-induced differential bioactive metabolites in the plasma samples of 20 patients at day 1 (time for basal metabolites) and day 7 (time for established chronic ischemic tolerance-associated metabolites) after onset of TIA. Mouse middle cerebral artery occlusion (MCAO)-induced stroke model was used to verify their prophylactic and therapeutic potentials. Transcriptomics changes in circulating neutrophils of patients with TIA were determined by RNA-sequencing. Multivariate statistics and integrative analysis of metabolomics and transcriptomics were performed to elucidate the potential mechanism of TIA-induced ischemic tolerance. Plasma metabolomics analysis identified five differentially upregulated metabolites associated with potentially TIA-induced ischemic tolerance, namely all-trans 13,14 dihydroretinol (atDR), 20-carboxyleukotriene B4, prostaglandin B2, cortisol and 9-KODE. They were associated with the metabolic pathways of retinol, arachidonic acid, and neuroactive ligand-receptor interaction. Prophylactic treatment of MCAO mice with these five metabolites significantly improved neurological functions. Additionally, post-stroke treatment with atDR or 9-KODE significantly reduced the cerebral infarct size and enhanced sensorimotor functions, demonstrating the therapeutic potential of these bioactive metabolites. Mechanistically, we found in patients with TIA that these metabolites were positively correlated with circulating neutrophil counts. Integrative analysis of plasma metabolomics and neutrophil transcriptomics further revealed that TIA-induced metabolites are significantly correlated with specific gene expression in circulating neutrophils which showed prominent enrichment in FoxO signaling pathway and upregulation of the anti-inflammatory cytokine IL-10. Finally, we demonstrated that the protective effect of atDR-pretreatment on MCAO mice was abolished when circulating neutrophils were depleted. TIA-induced potential ischemic tolerance is associated with upregulation of plasma bioactive metabolites which can protect against cerebral ischemic damage and improve neurological functions through a positive role of circulating neutrophils. National Natural Science Foundation of China (81974210), Science and Technology Planning Project of Guangdong Province, China (2020A0505100045), Natural Science Foundation of Guangdong Province (2019A1515010671), Science and Technology Program of Guangzhou, China (2023A03J0577), and Natural Science Foundation of Jiangxi, China（20224BAB216043).

Metabolomics reveals that PS-NPs promote lung injury by regulating prostaglandin B1 through the cGAS-STING pathway

Nanoplastics have been widely studied as environmental pollutants, which can accumulate in the human body through the food chain or direct contact. Research has shown that nanoplastics can affect the immune system and mitochondrial function, but the underlying mechanisms are unclear. Lungs and macrophages have important immune and metabolic functions. This study explored the effects of 100 nm PS-NPs on innate immunity, mitochondrial function, and cellular metabolism-related pathways in lung (BEAS-2B) cells and macrophages (RAW264.7). The results had shown that PS-NPs exposure caused a decrease in mitochondrial membrane potential, intracellular ROS accumulation, and Ca2+ overload, and activated the cGAS-STING signaling pathway related to innate immunity. These changes had been observed at concentrations of PS-NPs as low as 60 μg/mL, which might have been comparable to environmental levels. Non-target metabolomics and Western Blotting results confirmed that PS-NPs regulated prostaglandin B1 and other metabolites to cause cell damage through the cGAS-STING pathway. Supplementation of prostaglandin B1 alleviated the immune activation and metabolic disturbance caused by PS-NPs exposure. This study identified PS-NPs-induced innate immune activation, mitochondrial dysfunction, and metabolic toxicity pathways, providing new insights into the potential for adverse outcomes of NPs in human life.

Ecological benefits of artificial light at night (ALAN): Accelerating the development and metamorphosis of marine shellfish larvae

Urbanization has led to increasing use of artificial light at night (ALAN), which has rapidly become an important source of pollution in many cities. To identify the ALAN effects on the embryonic development of the Pacific abalone Haliotis discus hannai, we first exposed larvae to natural light with a light period of 12 L:12D (control, Group CTR). We then exposed larvae to three different light regimes. Larvae in Group NL were exposed to full spectrum artificial light from 18:00 to 00:00 to simulate the lighting condition at night, whereas Groups BL and YL were illuminated at the same time interval with 450 nm of short-wavelength blue light and 560 nm of long-wavelength orange light, respectively, to simulate billboard lighting at night. There were significantly higher hatching success and metamorphosis rates of larvae in Group BL than in Group YL or CTR (P < 0.05). The larvae in Group YL had the highest abnormality rate and took the longest time to complete metamorphosis. Transcriptomic studies revealed significantly higher expression levels of genes related to RNA transport, DNA replication, and protein processing in endoplasmic reticulum pathways in Group BL compared to the other groups. In the metabolomic analysis, we identified prostaglandin B1, tyramine, d-fructose 6-phosphate, L-adrenaline, leukotriene C4, and arachidonic acid as differential metabolic markers, as they play a vital part in helping larvae adapt to different ALAN conditions. Multi-omics correlation analysis of pairwise comparisons between all of the groups suggested that the biosynthesis of unsaturated fatty acids (FAs) and arachidonic acid metabolism pathways were significantly enriched (P < 0.05). Further quantitative analysis of the fatty acid (FA) contents revealed that 42 out of 50 FAs were down-regulated in Group BL and up-regulated in Group YL, which suggested that the synthesis, catabolism, and metabolism of FAs are crucial for the larval response to different spectral components of ALAN. For the first time, we report positive rather than negative effects of artificial blue light at night on the embryonic development of a benthic marine species. These results are significant for unbiased and full-scale assessment of the ecological effects of ALAN and for understanding the structural stability of the marine benthic community.

Effects of Aeromonas hydrophila infection on the intestinal microbiota, transcriptome, and metabolomic of common carp (Cyprinus carpio).

Aeromonas hydrophila frequently has harmful effects on aquatic organisms. The intestine is an important defense against stress. In this study, we investigated the intestinal microbiota and transcriptomic and metabolomic responses of Cyprinus carpio subjected to A. hydrophila infection. The results showed that obvious variation in the intestinal microbiota was observed after infection, with increased levels of Firmicutes and Bacteroidetes and decreased levels of Proteobacteria. Several genera of putatively beneficial microbiota (Cetobacterium, Bacteroides, and Lactobacillus) were abundant, while Demequina, Roseomonas, Rhodobacter, Pseudoxanthomonas, and Cellvibrio were decreased; pathogenic bacteria of the genus Vibrio were increased after microbiota infection. The intestinal transcriptome revealed several immune-related differentially expressed genes associated with the cytokines and oxidative stress. The metabolomic analysis showed that microbiota infection disturbed the metabolic processes of the carp, particularly amino acid metabolism. This study provides insight into the underlying mechanisms associated with the intestinal microbiota, immunity, and metabolism of carp response to A. hydrophila infection; eleven stress-related metabolite markers were identified, including N-acetylglutamic acid, capsidiol, sedoheptulose 7-phosphate, prostaglandin B1, 8,9-DiHETrE, 12,13-DHOME, ADP, cellobiose, 1H-Indole-3-carboxaldehyde, sinapic acid and 5,7-dihydroxyflavone.

Metabolomic and transcriptomic analysis reveals immune and hormone modulation at the molting stage of juvenile mud crabs challenged with Staphylococcus aureus and Vibrio alginolyticus

The mud crab (Scylla paramamosain) is an important economic breeding species along the southeast coast of China. As a crustacean, molting is critical for growth and reproduction. At each molting, a new external cuticle of mud crab is inherently regenerated, but along with molting the crabs are easily susceptible to pathogenic infection that might result in a low survival rate particularly at juvenile stages. To elucidate the potential response mechanism of juvenile mud crabs infected with bacteria in the molting process, integrated transcriptomic and metabolomic techniques were applied and the hormones, associated-hormone genes or immune genes modulated by challenge with Staphylococcus aureus or Vibrio alginolyticus were analyzed. The omic analysis showed that S. aureus or V. alginolyticus infection caused decreases in steroid hormones (cortisol, cortodoxone, cortisone, deoxycorticosterone) and fatty acid-derived hormones (prostaglandin A2, Δ17–6-keto prostaglandin F1α, 13,14-Dihydro-15-keto-tetranor prostaglandin F1α, prostaglandin B2, 2,3-Dinor-11β-prostaglandin F2α, thromboxane B2, and 11-Dehydro thromboxane B2). Correspondingly, transcriptomic analysis revealed that both S. aureus and V. alginolyticus infection downregulated the expression levels of fatty acid-derived hormone synthases. In addition, both bacterial infections caused upregulation in Toll, IMD, the Jak/Stat pathway, antimicrobial peptide, and the prophenoloxidase system. The study provides a new insight into the effects of bacteria on the juvenile crab molting process in vivo that lead to the modulation of both immune-associated genes and hormones.

Urinary microbiota and metabolic signatures associated with inorganic arsenic-induced early bladder lesions

Inorganic arsenic (iAs) contamination in drinking water is a global public health problem, and exposure to iAs is a known risk factor for bladder cancer. Perturbation of urinary microbiome and metabolome induced by iAs exposure may have a more direct effect on the development of bladder cancer. The aim of this study was to determine the impact of iAs exposure on urinary microbiome and metabolome, and to identify microbiota and metabolic signatures that are associated with iAs-induced bladder lesions. We evaluated and quantified the pathological changes of bladder, and performed 16S rDNA sequencing and mass spectrometry-based metabolomics profiling on urine samples from rats exposed to low (30 mg/L NaAsO2) or high (100 mg/L NaAsO2) iAs from early life (in utero and childhood) to puberty. Our results showed that iAs induced pathological bladder lesions, and more severe effects were noticed in the high-iAs group and male rats. Furthermore, six and seven featured urinary bacteria genera were identified in female and male offspring rats, respectively. Several characteristic urinary metabolites, including Menadione, Pilocarpine, N-Acetylornithine, Prostaglandin B1, Deoxyinosine, Biopterin, and 1-Methyluric acid, were identified significantly higher in the high-iAs groups. In addition, the correlation analysis demonstrated that the differential bacteria genera were highly correlated with the featured urinary metabolites. Collectively, these results suggest that exposure to iAs in early life not only causes bladder lesions, but also perturbs urinary microbiome composition and associated metabolic profiles, which shows a strong correlation. Those differential urinary genera and metabolites may contribute to bladder lesions, suggesting a potential for development of urinary biomarkers for iAs-induced bladder cancer.

Guominkang formula alleviate inflammation in eosinophilic asthma by regulating immune balance of Th1/2 and Treg/Th17 cells.

The number of patients with allergic asthma is rising yearly, and hormonal drugs, such as dexamethasone, have unique advantages and certain limitations. In the treatment of allergic diseases especially allergic asthma, increasing the percentage or the function of immunosuppressive cells, such as Treg cells, may achieve a good effect. On the basis of good clinical results, we found that Guominkang (GMK) especially high-concentration GMK can achieve a similar effect with dexamethasone in controlling the symptoms of allergic asthma and inhibiting inflammation of allergic asthma. In our study, GMK can inhibit the recruitment of inflammatory cells, decrease mucus production, and reduce airway resistance. Besides, GMK can reconstruct the cellular immune balance of Th1/2 and Treg/Th17 cells. Metabolome results show that DL-glutamine, L-pyroglutamic acid, prostaglandin b1, prostaglandin e2, and 3,4-dihydroxyhydrocinnamic acid are the metabolic biomarkers and are associated with Th1/2 and Treg/Th17 cell balance. GMK can also change the gut microbiota in the allergic asthma mouse model. The genus_Muriculum, genus_(Clostridium) GCA900066575, genus_klebsiella, genus_Desulfovibrio, genus_Rikenellaceae RC9 gut group, family_Chitinophagaceae, family_Nocardioidaceae, and genus_Corynebacterium are gut microbiota biomarkers treated by GMK. Among these biomarkers, genus_Muriculum is the gut microbiota biomarker associated with Th1/2 and Treg/Th17 cell balance. Interestingly, we first found that DL-glutamine, L-pyroglutamic acid, prostaglandin b1, prostaglandin e2, and 3,4-dihydroxyhydrocinnamic acid are all associated with genus_Muriculum. GMK will be a new strategy for the treatment of eosinophilic asthma, and biomarkers will also be a new research direction.

Fluoride exposure induces lysosomal dysfunction unveiled by an integrated transcriptomic and metabolomic study in bone marrow mesenchymal stem cells

Fluoride has received much attention for its predominant bone toxicity in the human body. However, the toxic mechanism of bone injury caused by fluoride exposure remains largely unclear. Bone marrow mesenchymal stem cells (BMSCs) are widely used as model cells for evaluating bone toxicity after environmental toxicant exposure. In this study, BMSCs were exposed to fluoride at 1, 2, and 4 mM for 24 h, and fluoride significantly inhibited cell viability at 2 and 4 mM. A multiomics analysis combining transcriptomics with metabolomics was employed to detect alterations in genes and metabolites in BMSCs treated with 2 mM fluoride. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of transcriptomics profiles identified “lysosomes” as the top enriched pathway, which was severely damaged by fluoride exposure. Lysosomal damage was indicated by decreases in the expression of lysosomal associated membrane protein 2 (LAMP 2) and cathepsin B (CTSB) as well as an increase in pH. Upregulation of the lysosome-related genes Atp6v0b and Gla was observed, which may be attributed to a compensatory lysosomal biogenesis transcriptional response. Interestingly, inhibition of glutathione metabolism was observed in fluoride-treated BMSCs at the metabolomic level. Moreover, an integrative analysis between altered genes, metabolites and lysosome signaling pathways was conducted. Palmitic acid, prostaglandin C2, and prostaglandin B2 metabolites were positively associated with Atp6v0b, a lysosome-related gene. Overall, our results provide novel insights into the mechanism responsible for fluoride-induced bone toxicity.

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease.

Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD.

Serum Metabolomics Analysis for Biomarkers of Lactobacillus plantarum FRT4 in High-Fat Diet-Induced Obese Mice

Lactobacillus plantarum is considered a potential probiotic supplementation for treating obesity. However, the underlying molecular mechanism is poorly understood. Our previous study displayed that L. plantarum FRT4 alleviated obesity in mice fed a high-fat diet (HFD) through ameliorating the HFD-induced gut microbiota dysbiosis. To explore the roles of FRT4 in obesity prevention, in this study, we investigated changes in serum metabolomic phenotype by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and analyzed the pathway of HFD-fed Kunming female mice orally administered with FRT4 for eight weeks. Using orthogonal partial least squares discriminant analysis (OPLS-DA), metabolite patterns with significant changes were observed. 55 metabolites including phosphatidylcholine, lysophophatidylcholine, sphingomyelin, serotonin, indole-3-methyl aceta, indole-3-carbinol, indole-5,6-quino, 11,12-DHET, prostaglandin B2, leukotriene B4, and 3-hydroxybenzoic acid were identified as potential biomarkers associated with obesity, which were mainly involving in glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. Perturbations of 14 biomarkers could be regulated by FRT4 intervention. These metabolites may serve as valuable biomarkers to understand the mechanisms by which intake of diets containing FRT4 contributes to the treatment or prevention of obesity. Thus, FRT4 can be a promising dietary supplement for the prevention of HFD-induced obesity.

Exploring the mechanism of Yixinyin for myocardial infarction by weighted co-expression network and molecular docking

Yixinyin, the traditional Chinese medicine, has the effects of replenishing righteous qi, and promoting blood circulation to eliminate blood stagnation. It is often used to treat patients with acute myocardial infarction (MI). The purpose of our study is to explore the key components and targets of Yixinyin in the treatment of MI. In this study, we analyzed gene expression data and clinical information from 248 samples of MI patients with the GSE34198, GSE29111 and GSE66360 data sets. By constructing a weighted gene co-expression network, gene modules related to myocardial infarction are obtained. These modules can be mapped in Yixinyin PPI network. By integrating differential genes of healthy/MI and unstable angina/MI, key targets of Yixinyin for the treatment of myocardial infarction were screened. We validated the key objectives with external data sets. GSEA analysis is used to identify the biological processes involved in key targets. Through molecular docking screening, active components that can combine with key targets in Yixinyin were obtained. In the treatment of myocardial infarction, we have obtained key targets of Yixinyin, which are ALDH2, C5AR1, FOS, IL1B, TLR2, TXNRD1. External data sets prove that they behave differently in the healthy and MI (P < 0.05). GSEA enrichment analysis revealed that they are mainly involved in pathways associated with myocardial infarction, such as viral myocarditis, VEGF signaling pathway and type I diabetes mellitus. The docking results showed that the components that can be combined with key targets in YixinYin are Supraene, Prostaglandin B1, isomucronulatol-7,2′-di-O-glucosiole, angusifolin B, Linolenic acid ethyl ester, and Mandenol. For that matter, they may be active ingredients of Yixinyin in treating MI. These findings provide a basis for the preliminary research of myocardial infarction therapy in traditional Chinese medicine and provide ideas for the design of related drugs.

Network Pharmacology and Molecular Docking-Based Analysis on Bioactive Anticoronary Heart Disease Compounds in Trichosanthes kirilowii Maxim and Bulbus allii Macrostemi.

Trichosanthes kirilowii Maxim. and Bulbus allii Macrostemi are the components of Gualou Xiebai decoction (GLXB), a commonly used herbal combination for the treatment of coronary heart disease (CHD) in traditional Chinese medicine. Although GLXB is associated with a good clinical effect, its active compounds and mechanism of action remain unclear, which limits its clinical application and the development of novel drugs. In this study, we explored key compounds, targets, and mechanisms of action for GLXB in the treatment of CHD using the network pharmacology approach. We identified 18 compounds and 21 action targets via database screening. Enrichment analysis indicated that the effects of GLXB in patients with CHD are primarily associated with the regulation of signalling pathways for tumour necrosis factor, nuclear factor-kappa B, hypoxia-inducible factor-1, arachidonic acid metabolism, and insulin resistance. GLXB thus exerts anti-inflammatory, antihypoxic, and antiagglutinating effects; regulates lipid metabolism; and combats insulin resistance in CHD via these pathways, respectively. After reverse targeting, we observed that the main active compounds of GLXB in the treatment of CHD were quercetin, naringenin, β-sitosterol, ethyl linolenate, ethyl linoleate, and prostaglandin B1. To explore the potential of these compounds in the treatment of CHD, we verified the affinity of the compounds and targets via molecular docking analysis. Our study provides a bridge for the transformation of natural herbs and molecular compounds into novel drug therapies for CHD.

Increased Epoxyeicosatrienoic Acids and Hydroxyeicosatetraenoic Acids After Treatment of Iodide Intake Adjustment and 1,25-Dihydroxy-Vitamin D3 Supplementation in High Iodide Intake-Induced Hypothyroid Offspring Rats.

Aim: This study aimed to investigate the potential role of fatty acids in high iodide intake–induced hypothyroidism and its complications and also in the intervention of iodide intake adjustment and 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] supplementation.Methods: Pregnant rats were allocated to two groups, namely, normal iodide (NI, 7.5 μg/day) intake and 100 times higher-than-normal iodide (100 HI, 750 μg/day) intake. The offspring were continuously administered potassium iodide from weaning [i.e., postnatal day 21 (PN21)] to PN90. After PN90, the offspring were either administered iodide intake adjustment (7.5 μg/day) or 1,25(OH)2D3 supplementation (5 μg·kg−1·day−1), or both, for 4 weeks. Thyroid function tests (free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibody, and thyroglobulin antibody), blood lipids (triglyceride, total cholesterol, free fatty acid, and low-density lipoprotein cholesterol), and vitamin D3 (VD3) levels were detected by ELISA. Cardiac function was measured by echocardiography. Blood pressure was measured using a non-invasive tail-cuff system. The serum fatty acids profile was analyzed by liquid chromatography–mass spectrometry.Results: In the offspring rats with continued 100 HI administration, the levels of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET) and thromboxane B2 (TXB2) were decreased, while those of prostaglandin J2 (PGJ2), prostaglandin B2 (PGB2), 4-hydroxydocosahexaenoic acid (4-HDoHE), 7-HDoHE, 8-HDoHE, and 20-HDoHE were increased. Significant correlations were found between PGB2, 8,9-DHET, 7-HDoHE levels and thyroid dysfunction, between PGJ2, 20-HDoHE, PGB2, 8,9-DHET levels and cardiac dysfunction, between PGJ2, 20-HDoHE levels and hypertension, between 4-HDoHE, 8-HDoHE, TXB2 levels and dyslipidemia, and between PGB2 and decreased VD3 level. After the treatment of iodide intake adjustment and 1,25(OH)2D3 supplementation, the levels of 16-hydroxyeicosatetraenoic acids (16-HETE), 18-HETE, 5,6-epoxyeicosatrienoic acid (5,6-EET), 8,9-EET, 11,12-EET, 14,15-EET, PGE2, 5-oxo-ETE, and 15-oxo-ETE were increased. The significant associations between PGE2, 16-HETE, 18-HETE and improved thyroid function and also between 5,6-EET, 11,12-EET, 14,15-EET, 16-HETE, 15-oxo-ETE and attenuated dyslipidemia were detected.Conclusion: Increased levels of prostaglandins (PGs) and HDoHEs and decreased levels of 8,9-DHET and TXB2 might occur in the progression of cardiac dysfunction, hypertension, and dyslipidemia in high iodide intake–induced hypothyroidism. The increased levels of EETs and HETEs might help to ameliorate these complications after iodide intake adjustment and 1,25(OH)2D3 supplementation.

Allergens and their associated small molecule ligands-their dual role in sensitization.

Many allergens feature hydrophobic cavities that allow the binding of primarily hydrophobic small‐molecule ligands. Ligand‐binding specificities can be strict or promiscuous. Serum albumins from mammals and birds can assume multiple conformations that facilitate the binding of a broad spectrum of compounds. Pollen and plant food allergens of the family 10 of pathogenesis‐related proteins bind a variety of small molecules such as glycosylated flavonoid derivatives, flavonoids, cytokinins, and steroids in vitro. However, their natural ligand binding was reported to be highly specific. Insect and mammalian lipocalins transport odorants, pheromones, catecholamines, and fatty acids with a similar level of specificity, while the food allergen β‐lactoglobulin from cow's milk is notably more promiscuous. Non‐specific lipid transfer proteins from pollen and plant foods bind a wide variety of lipids, from phospholipids to fatty acids, as well as sterols and prostaglandin B2, aided by the high plasticity and flexibility displayed by their lipid‐binding cavities. Ligands increase the stability of allergens to thermal and/or proteolytic degradation. They can also act as immunomodulatory agents that favor a Th2 polarization. In summary, ligand‐binding allergens expose the immune system to a variety of biologically active compounds whose impact on the sensitization process has not been well studied thus far.

Transcriptomic and metabolomic insights into the variety of sperm storage in oviduct of egg layers

In birds, the sperm storage tubules (SST) are dispersed in uterovaginal junction (UVJ) and highly correlated with differential capacity of sperm storage (SS) in and among species with unspecified mechanisms. Here, the SS duration of 252 egg layer breeders was evaluated in 5 rounds with 3 phenotypic traits to screen high- and low-SS individuals, respectively, followed with transcriptome of UVJ tissues and metabolome of serum (high-SS vs. low-SS) to decipher the candidate genes and biochemical markers correlated with differential SS capacity. Histological characterization suggested slightly higher density of SST in UVJ (high-SS vs. low-SS). Transcriptome analyses identified 596 differentially expressed genes (336 upregulated vs. 260 downregulated), which were mainly enriched in gene ontology terms of homeostasis, steroid and lipid metabolism and hormone activity, and 12 significant pathways (P < 0.05) represented by calcium, steroid, and lipid metabolism. Immunohistochemical staining of GNAQ, ST6GAL1, ADFP, and PCNA showed similar distribution in UVJ tissues between 2 groups. Several candidates (HSD11B2, DIO2, AQP3, GNAQ, NANS, ST6GAL1) combined with 4 (11β-prostaglandin F2α, prostaglandin B1, 7α-hydroxytestosterone, and N-acetylneuraminic acid) of 40 differential metabolites enriched in serum metabolome were considered as regulators and biomarkers of SS duration in egg layer breeders. The integrated transcriptome and metabolome analyses of chicken breeder hens will provide novel insights for exploration and improvement of differential SS capacity in birds.

Research on serum metabolomics of ovariectomized rats and intervention effect of Cuscuta chinensis on metabolic pattern

As a traditional Chinese medicine of invigorating the kidney, Cuscuta chinensis (CC) can be applied in improving the deficiency of kidney qi in menopausal women and regulating the level of estrogen. Previously, it was found that the ethanol extract of CC had an estrogen-like effect. In this study, the metabolic profile and metabolic pathways of rats in sham, ovariectomized model and CC groups were analyzed using UPLC-TOFMS-based metabolomics and the pattern recognition technology. The serum endogenouse metabolites could be well differentiated in different group, indicating significant differences of metabolic profiles. CC had an reverse adjustment effect on 14 differential metabolites of ovariectomized rats, including sinapyl alcohol, deoxycholic acid, prostaglandin B2, prostaglandin I2, dihydrosphingosine, choline, pentadecanoic acid, arachidonic acid, 1-stearoyl-Sn-Glycerol-3-Phosphocholine, palmitoleic acid, palmitic acid, vaccenic acid, oleic acid and stearic acid. Furthermore, these differential metabolites were categorized into several major pathways, such as biosynthesis of unsaturated fatty acids, lycerophospholipid metabolism and arachidonic acid metabolism. Therefore, it could be concluded that the estrogen-like effect of CC was related to the lipid metabolism to some extent. The research results provide useful help for the in-depth research and development of CC.

Distinct Gut Microbiota and Metabolite Profiles Induced by Different Feeding Methods in Healthy Chinese Infants.

Human milk is closely correlated with infant gut microbiota and is important for infant development. However, most infants receive exclusively insufficient breast milk, and the discordance between effects of commercial formula and human milk exists. To elucidate the differences induced by various feeding methods, we determined microbiota and metabolites composition in fecal samples from 77 healthy infants in Northeast China and identified the differences in various feeding methods. Bacterial 16S rRNA gene sequence analysis demonstrated that the fecal samples of exclusively breastfed (BF) infants were abundant in Bifidobacterium and Lactobacillus; the mixed-fed (MF) infants had the highest abundance of Veillonella and Klebsiella; the exclusively formula-fed (FF) infants were enriched in Bacteroides and Blautia; and the complementary food-fed (CF) infants were associated with higher relative abundance of Lachnoclostridium and Akkermansia. Liquid chromatography–mass spectrometry (LC-MS)-based metabolomics data revealed that the fecal samples of BF infants had the highest abundance of dl-citrulline, threonine, l-proline, l-glutamine, guanine, and l-arginine; the MF infants were abundant in d-maltose, stearidonic acid, capric acid, and myristic acid; the FF infants were enriched in itaconic acid, 4-pyridoxic acid, prostaglandin B2, thymine, dl-α-hydroxybutyric acid, and orotic acid; and the CF infants were associated with higher relative abundance of taurine, l-tyrosine, adenine, and uric acid. Furthermore, compared with the BF infants, the MF and FF infants were more abundant in fatty acid biosynthesis. Collectively, these findings will provide probable explanations for some of the risks and benefits related to infant feeding methods and will support a theoretical basis for the development of infant formula.