Regulation Of Amino Acid Metabolism Research Articles

Photothermal Lysis of Engineered Bacteria to Modulate Amino Acid Metabolism against Tumors

AbstractBacterial‐mediated synergistic cancer therapy (BMSCT) is used as a promising tumor therapy approach. However, there are some disadvantages of bacterial therapy alone to be resolved, such as low tumor suppression rate in the treatment. In this study, a novel light‐controlled engineered bacterial material which synergistically regulates amino acid metabolism to fight tumors is developed. It transcribes l‐methionine‐γ‐lyase (MdeA) into Escherichia coli (E. coli) and loads the approved photothermal agent indocyanine green (ICG), namely E. coli‐MdeA@ICG. Using the hypoxic tropism of E. coli, genetically engineered bacteria are first loaded with photothermal agents, then selectively accumulate and replicate in the tumor region. Under laser irradiation, photothermal lysis of E. coli‐MdeA is performed to release the MdeA and consume the essential amino acid methionine (Met) in the tumor environment. In vitro cell experiments confirm that the E. coli‐MdeA + NIR group can reach 90% of the 4T1 cells killing. In 4T1 tumor‐bearing mouse models, E. coli‐MdeA@ICG shows enhanced antitumor efficacy, along with 91.8% of the tumor growth inhibited. Apoptosis of tumor cells is induced under the dual action of photothermal therapy (PTT) and amino acid metabolism therapy. This strategy provides new ideas for the combination of synthetic biology and nanotechnology in anti‐tumor.

Metabolic and transcriptional responses demonstrating enhanced thermal tolerance in domesticated abalone

Global warming threatens aquatic systems and organisms. Many studies have focused on the vulnerability and stress responses of aquaculture organisms to future thermal conditions. However, it may be of more practical significance to reveal their acclimation potential and mechanisms. In this study, the physiological, metabolic, and transcriptional responses to long-term temperature acclimation of northern and southern populations of Pacific abalone Haliotis discus hannai, a commercially important gastropod sensitive to environmental changes, were compared. This study conducted two common-garden experiments, including a thermostatic experiment in the lab and an aquaculture experiment on the farm. The abalone population cultured in warmer southern waters was tolerant of ongoing high temperatures, whereas the abalone population originally cultured in cooler northern waters exhibited vulnerability to high temperatures but could enhance its thermal tolerance through the process of natural selection in warmer southern waters. This difference was linked to divergence in the metabolic and transcriptional processes of the two populations. The tolerant population exhibited a greater capacity for carbohydrate and amino acid metabolism regulation and energy redistribution to cope with heat stress. This capacity may have been selected for, and accumulated, over many generations because the tolerant population originated from the intolerant population over two decades ago. This work provides insight into the vulnerability and acclimation potential of abalone to heat stress and discloses the molecular and metabolic traits underlying this phenomenon. Future research on the ability of abalone and other commercial shellfish species to acclimate to global warming should take this potential into account.

Hypolipidemic mechanism of Pleurotus eryngii polysaccharides in high-fat diet-induced obese mice based on metabolomics.

In this study, the structure of Pleurotus eryngii polysaccharides (PEPs) was characterized, and the mechanism of PEP on obesity and hyperlipidemia induced by high-fat diet was evaluated by metabonomic analysis. The structure of PEPs were characterized by monosaccharide composition, Fourier transform infrared spectroscopy and thermogravimetry. In animal experiments, H&E staining was used to observe the morphological difference of epididymal adipose tissue of mice in each group. Ultrahigh performance liquid chromatography (UHPLC)-(QE) HFX -mass spectrometry (MS) was used to analyze the difference of metabolites in serum of mice in each group and the related metabolic pathways. The PEPs contained nine monosaccharides: 1.05% fucose, 0.30% arabinose, 17.94% galactose, 53.49% glucose, 1.24% xylose, 23.32% mannose, 1.30% ribose, 0.21%galacturonic acid, and 1.17% glucuronic acid. The PEPs began to degrade at 251°C (T0), while the maximum thermal degradation rate temperature (Tm) appeared at 300°C. The results histopathological observation demonstrated that the PEPs had signifificant hypolipidemic activities. After PEPs intervention, the metabolic profile of mice changed significantly. A total of 29 different metabolites were selected as adjunctive therapy to PEPs, for treatment of obesity and hyperlipidemia-related complications caused by a high-fat diet. These metabolites include amino acids, unsaturated fatty acids, choline, glycerol phospholipids, and other endogenous compounds, which can prevent and treat obesity and hyperlipidemia caused by a high-fat diet by regulating amino acid metabolism, fatty acid metabolism, and changes in metabolic pathways such as that involved in the citric cycle (TCA cycle). The presented results indicate that PEPs treatment can alleviate the obesity and hyperlipidemia caused by a high-fat diet and, thus, may be used as a functional food adjuvant, providing a theoretical basis and technical guidance for the prevention and treatment of high-fat diet-induced obesity and hyperlipidemia.

Targeted metabolomics analysis identified the role of FOXA1 in the change in glutamate-glutamine metabolic pattern of BaP malignantly transformed 16HBE cells

The carcinogenic mechanism of benzo[a]pyrene (BaP) is far from being elucidated. FOXA1 has been confirmed to play an oncogenic role in BaP-transformed cell THBEc1. To explore the changes in amino acid metabolic patterns, especially glutamate-glutamine (Glu-Gln) metabolic pattern caused by BaP-induced transformation and the possible role FOXA1 might play in it, we compared amino acid metabolic characteristics between THBEc1 cells and control 16HBE cells using a targeted metabolomics method and determined the effects of FOXA1 knockout on the amino acid metabolic pattern using FOXA1 knockout cell THBEc1-ΔFOXA1-c34. The amino acid metabolic patterns of THBEc1 and 16HBE cells were different, which was manifested by the differential consumption of 18 amino acids and the difference in the intracellular content of 21 amino acids. The consumption and intracellular content of Glu and Gln are different between the two types of cells, accompanied by upregulation of FOXA1, GLUL, SLC1A3, SLC1A4, SLC1A5 and SLC6A14, and downregulation of FOXA2 and GPT2 in THBEc1 cells. FOXA1 knockout changed the consumption of 19 amino acids and the intracellular content of 21 amino acids and reversed the metabolic pattern of Glu and the changes in FOXA2, GLUL, SLC1A3 and SLC6A14 in THBEc1 cells. Additionally, FOXA1 knockout inhibited cell proliferation and further increased the dependence of THBEc1 cells on Glu. In conclusion, FOXA1 knockout partially reversed the change in Glu-Gln metabolism caused by BaP-induced transformation by upregulating the expression of GLUL and SLC1A3. Our findings provide a clue for the possible role of FOXA1 in amino acid metabolism regulation.

Single-cell RNA sequencing reveals the suppressive effect of PPP1R15A inhibitor Sephin1 in antitumor immunity

Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) is an important factor in the integrated stress response (ISR) in mammals and may play a crucial role in tumorigenesis. In our studies, we found an inhibitor of PPP1R15A, Sephin1, plays a protumorigenic role in mouse tumor models. By analyzing the single-cell transcriptome data of the mouse tumor models, we found that in C57BL/6 mice, Sephin1 treatment could lead to higher levels of ISR activity and lower levels of antitumor immune activities. Specifically, Sephin1 treatment caused reductions in antitumor immune cell types and lower expression levels of cytotoxicity-related genes. In addition, Tcell receptor (TCR) repertoire analysis demonstrated that the clonal expansion of tumor-specific Tcells was inhibited by Sephin1. A special TCR+ macrophage subtype in tumor was identified to be significantly depleted upon Sephin1 treatment, implying its key antitumor role. These results suggest that PPP1R15A has the potential to be an effective target for tumor therapy.

Identification of Protective Amino Acid Metabolism Events in Nursery Pigs Fed Thermally Oxidized Corn Oil.

Feeding thermally oxidized lipids to pigs has been shown to compromise growth and health, reduce energy digestibility, and disrupt lipid metabolism. However, the effects of feeding oxidized lipids on amino acid metabolism in pigs have not been well defined even though amino acids are indispensable for the subsistence of energy metabolism, protein synthesis, the antioxidant system, and many other functions essential for pig growth and health. In this study, oxidized corn oil (OCO)-elicited changes in amino acid homeostasis of nursery pigs were examined by metabolomics-based biochemical analysis. The results showed that serum and hepatic free amino acids and metabolites, including tryptophan, threonine, alanine, glutamate, and glutathione, as well as associated metabolic pathways, were selectively altered by feeding OCO, and more importantly, many of these metabolic events possess protective functions. Specifically, OCO activated tryptophan-nicotinamide adenosine dinucleotide (NAD+) synthesis by the transcriptional upregulation of the kynurenine pathway in tryptophan catabolism and promoted adenine nucleotide biosynthesis. Feeding OCO induced oxidative stress, causing decreases in glutathione (GSH)/oxidized glutathione (GSSG) ratio, carnosine, and ascorbic acid in the liver but simultaneously promoted antioxidant responses as shown by the increases in hepatic GSH and GSSG as well as the transcriptional upregulation of GSH metabolism-related enzymes. Moreover, OCO reduced the catabolism of threonine to α-ketobutyrate in the liver by inhibiting the threonine dehydratase (TDH) route. Overall, these protective metabolic events indicate that below a certain threshold of OCO consumption, nursery pigs are capable of overcoming the oxidative stress and metabolic challenges posed by the consumption of oxidized lipids by adjusting antioxidant, nutrient, and energy metabolism, partially through the transcriptional regulation of amino acid metabolism.

Effects of low-energy diet supplemented with betaine on growth performance, nutrient digestibility, and serum metabolomic profiles in growing pigs.

Two experiments were carried out to evaluate the effects of betaine (BET) supplementation in diets with reduced net energy (NE) levels on growth performance, nutrient digestibility, and serum metabolomic profiles in growing pigs. In experiment 1, 24 growing pigs (initial body weight, BW, 30.83 ± 2.50 kg) were allotted to one of the four treatments (six replications with 1 pig per pen) in a 2 × 2 factorial arrangement, including two dietary NE levels (2475 [N-NE] or 2395 [R80-NE] kcal/kg) and two BET doses (0 or 1500 mg/kg). In experiment 2, 72 growing pigs were used in a 2 × 3 factorial arrangement, including three dietary NE levels (2475 [N-NE], 2415 [R60-NE], or 2355 [R120-NE] kcal/kg) and two BET doses (0 or 1500 mg/kg). Pigs with initial BW of 31.44 ± 1.65 kg were divided to one of the six treatments (six replications with 2 pigs per pen). In experiment 1, lowing NE concentrations increased average daily feed intake (ADFI) by 10.69% in pigs fed the diet without BET (P > 0.05). BET significantly increased ADFI in N-NE diet (P < 0.05) but had no influence on ADFI in R80-NE diet (P > 0.05). BET enhanced the apparent digestibility of crude protein (CP), dry matter (DM), organic matter (OM), gross energy (GE), and ether extract (EE) in R80-NE diet (P < 0.05). In experiment 2, lowing NE concentrations enhanced ADFI (P > 0.05) and decreased average daily gain (ADG; P < 0.05). The reduction in feed intake by BET was further enhanced as NE concentrations decreased from 2415 to 2355 kcal/kg (P < 0.10). BET reversed the elevation of serum triglyceride, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels caused by R120-NE diet (P < 0.05). The concentrations of cholecystokinin and glucagon-like peptide 1 were increased by BET in pigs fed the R120-NE diet (P < 0.05). Serum metabolomics reveals that lowing dietary NE concentrations affected mainly amino acid biosynthetic pathways (P < 0.05). BET supplementation in R120-NE diet up-regulated serum BET levels and down-regulated homocysteine, DL-carnitine, and four amino acid secondary metabolites (P < 0.05). In conclusion, lowing dietary NE contents reduced the growth performance and caused metabolic abnormalities in growing pigs. However, BET decreased feed intake to a certain extent and improved the metabolic health of pigs fed the low-NE diets, which may be related to the dual regulation of amino acid metabolism and the secretion of appetite related hormones by BET.

Mechanistic insights into the improvement of yeast viability by adding short-clustered maltodextrin during long-term frozen storage

The formation and growth of ice crystals are widely acknowledged to cause damage to different substances and we found short-clustered maltodextrin (SCMD) could alleviate the quality deterioration of frozen dough in previous research. But how SCMD interacts with dough components such as yeast is poorly understood. Here, we analyze the ice-recrystallization-inhibition (IRI) activity of SCMD and provide mechanistic insights into the improvement of yeast viability by adding SCMD during long-term frozen storage. SCMD had a higher IRI activity compared with DE2 maltodextrin, trehalose and glycerin at the same dosage. Through untargeted metabolomics analysis, SCMD addition proved to be enhancing lipid metabolism, regulating amino acid metabolism and energy metabolism of yeast, making yeast cells possess more similarities to the positive control with minimal freeze injury. In contrast, no significant protective effects were observed with low-concentration trehalose and glycerin. Our reports reveal the cryoprotection mechanism of SCMD from the perspective of the cellular metabolism of yeast, providing the foothold for further exploration of SCMD as a safe and efficient cryoprotectant in different fields. • Short-clustered maltodextrin (SCMD) could change ice-crystal shapes. • SCMD had a higher ice-recrystallization-inhibition (IRI) activity than trehalose and glycerin at the same dosage. • SCMD addition could improve yeast viability and fermentation ability during long-term frozen storage. • SCMD addition enhanced lipid metabolism, regulated amino acid metabolism and energy metabolism of yeast. • SCMD cryoprotection mechanism was proposed.

WZ35 inhibits gastric cancer cell metastasis by depleting glutathione to promote cellular metabolic remodeling

This study aimed at elucidating the crosstalk between redox reaction and metabolic remodeling through uncovering the mechanism underlying WZ35-mediated reactive oxygen species (ROS) production and regulation of amino acid metabolism to inhibit gastric cancer (GC) cell metastasis. The activity and biosafety of curcumin analog, WZ35, were verified in vitro and in vivo. The potential molecular mechanism underlying WZ35-mediated enhanced radiotherapeutic sensitivity by reduced Glutathione (GSH) depletion was elucidated by RNA sequencing, single-cell sequencing (scRNA-seq), metabolic mass spectrometry, and other molecular experiments. Compared to curcumin, WZ35 proved more potent anti-proliferative and anti-metastasis properties. Importantly, we demonstrated that WZ35 could consume GSH in multiple ways, including by reduction of raw materials and consumption reserves, inhibition of reformation, and enhanced decomposition. Mechanistically, we identify that WZ35 maintains the GSH depletion phenotype through the ROS-YAP-AXL-ALKBH5-GLS2 loop, further backing the relevance of metabolic remodeling in the tumor microenvironment with tumor metastasis and the role of m6A in tumor metastasis. Collectively, our study identified WZ35 as a novel GSH depletion agent and a previously undiscovered GSH depletion loop mechanism in GC cell metastasis.

Comprehensive analysis of the amino acid metabolism-related gene signature for prognosis, tumor immune microenvironment, and candidate drugs in hepatocellular carcinoma.

Metabolic rewiring satisfies increased nutritional demands and modulates many oncogenic processes in tumors. Amino acid metabolism is abnormal in many malignancies. Metabolic reprogramming of amino acids not only plays a crucial role in sustaining tumor cell proliferation but also influences the tumor immune microenvironment. Herein, the aim of our study was to elucidate the metabolic signature of amino acids in hepatocellular carcinoma (HCC). Transcriptome profiles of HCC were obtained from the TCGA and ICGC databases. Based on the expression of amino acid metabolism-related genes (AAMRGs), we clustered the HCC samples into two molecular subtypes using the non-negative matrix factorization algorithm. Then, we constructed the amino acid metabolism-related gene signature (AAMRGS) by Cox regression and LASSO regression. Afterward, the clinical significance of the AAMRGS was evaluated. Additionally, we comprehensively analyzed the differences in mutational profiles, immune cell infiltration, immune checkpoint expression, and drug sensitivity between different risk subgroups. Furthermore, we examined three key gene expressions in liver cancer cells by quantitative real-time PCR and conducted the CCK8 assay to evaluate the influence of two chemotherapy drugs on different liver cancer cells. A total of 81 differentially expressed AAMRGs were screened between the two molecular subtypes, and these AAMRGs were involved in regulating amino acid metabolism. The AAMRGS containing GLS, IYD, and NQO1 had a high value for prognosis prediction in HCC patients. Besides this, the two AAMRGS subgroups had different genetic mutation probabilities. More importantly, the immunosuppressive cells were more enriched in the AAMRGS-high group. The expression level of inhibitory immune checkpoints was also higher in patients with high AAMRGS scores. Additionally, the two AAMRGS subgroups showed different susceptibility to chemotherapeutic and targeted drugs. In vitro experiments showed that gemcitabine significantly reduced the proliferative capacity of SNU449 cells, and rapamycin remarkedly inhibited Huh7 proliferation. The five HCC cells displayed different mRNA expression levels of GLS, IYD, and NQO1. Our study explored the features of amino acid metabolism in HCC and identified the novel AAMRGS to predict the prognosis, immune microenvironment, and drug sensitivity of HCC patients. These findings might help to guide personalized treatment and improve the clinical outcomes of HCC.

Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure.

Heart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates. Jiashen tablets (JST), a Chinese herbal formula, have been reported to be an effective treatment against heart failure, however the underlying mechanisms remain obscure. This study was designed to determine the effect of JST on the treatment of heart failure and delineate the underlying mechanisms by an untargeted metabolomics approach. The chronic heart failure model was established by the permanent ligation of the left anterior descending coronary artery in rats. The cardiac functions of rats, including left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular internal diameter end diastole (LVIDd) and end systole (LVIDs), and interventricular septum thickness in diastole (IVSd) and in systole (IVSs), were measured by echocardiography. Biochemical analysis and histopathological examination were also performed to evaluate therapeutic effects of JST for treating heart failure. UHPLC-QTOF-MS/MS coupled with multivariate statistical analyses were applied for plasma metabolic profiling to identify biomarkers and potential mechanisms of JST in the treatment of heart failure. Jiashen tablets could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF and LVFS and decreasing LVIDd, LVIDs, IVSd, and IVSs. Results of biochemical analysis and histopathological examination revealed that JST could reduce the serum lactate dehydrogenase (LDH) activity and the level of NT-pro BNP, markers of heart failure and myocardial damage, and inhibit myocardial fibrosis. Furthermore, in metabolomics analysis, a total of 210 metabolites with significant differences were identified between heart failure rats and normal rats, among which 29 metabolites were significantly restored after JST treatment. These metabolites were primarily involved in tryptophan metabolism, branched-chain amino acid metabolism, fatty acids β-oxidation, and glycerophospholipid metabolism. The present study illustrated the therapeutic effect of JST for the treatment of heart failure and delineated the underlying mechanisms mainly relating to the regulation of amino acid metabolism and lipid metabolism in heart failure rats.

Potential mechanisms of Lian-Zhi-Fan solution for TNBS-induced ulcerative colitis in rats via a metabolomics approach.

Lian-Zhi-Fan (LZF) decoction is a hospital-prescribed traditional Chinese medicine botanical drug prepared by the fermentation of decocted Coptidis Rhizome (Huanglian), Gardeniae Fructus (Zhizi), and alum (Baifan). It has been used clinically in China for the treatment of anal fistula, perianal abscess, ulcerative colitis (UC), and other anorectal diseases for hundreds of years. However, due to the complexity of traditional Chinese medicine, the potential mechanisms of LZF in the treatment of UC have remained unknown. This study primarily investigated the remarkable pharmacological effects of LZF on TNBS-induced UC rats. To explore the complex targets and regulatory mechanisms of metabolic networks under LZF intervention, a metabolomics approach mediated by HPLC/Q-TOF-MS analysis was used to screen the different metabolites and their metabolic pathways in the serum in order to characterize the possible anti-UC mechanisms of LZF. After rectal administration of LZF for seven consecutive days, significant amelioration effects on body weight loss, DAI score, and colon inflammation were found in UC rats. Based on this, further metabolomics identified 14 potential biomarkers in the treatment of UC with LZF, of which five possessed diagnostic significance: L-alanine, taurocholic acid, niacinamide, cholic acid, and L-valine. These metabolites are mainly involved in 12 metabolic pathways, including nicotate and nicotinamide metabolism, glycospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and pantothenate and CoA biosynthesis. These metabolic pathways suggest that LZF ameliorates UC by regulating amino acid metabolism, fat metabolism, and energy production. This study provides a useful approach for exploring the potential mechanisms of herbal prescription in UC treatment mediated by metabolomics.

Regulation of Amino Acid Metabolism in Hematological Malignancies: Advances from Transcriptomics and Metabolomics

Tumor cells use amino acids to rewire metabolic pathways to meet increased demands for energy, reducing equivalents, and cellular biosynthesis. Aside acting as building blocks for protein synthesis, amino acids also function as metabolic intermediates for ATP generation and redox homeostasis, as well as fueling biosynthetic pathways. Tumor-related metabolic changes influence every stage of the interaction between cells and their metabolites. Over the years, advancements in molecular methods such as transcriptomics and metabolomics have emerged to provide in-depth knowledge into the functions, interactions, and actions of molecules in cells of organisms. These technologies surfaced as methods that provide a more complete picture of disease pathophysiology, facilitating the elucidation of disease mechanisms and identification of potential biomarkers (metabolites) and targets (genes) respectively. Though Omics in cancer research have been explored in different concepts, however, employing these methods in amino acid metabolism in hematological cancers still requires attention. Therefore, this mini review discusses an up-to-date knowledge of principal regulators and their role in amino acid metabolism in hematological malignancies. In that perspective, we cover relevant findings from transcriptomics and metabolomics, thereby constructing mechanistic insights associated with disease pathogenesis.

Multi-omics analyses reveal new insights into nutritional quality changes of alfalfa leaves during the flowering period.

High-quality alfalfa is an indispensable resource for animal husbandry and sustainable development. Its nutritional quality changes dramatically during its life cycle and, at present, no molecular mechanisms for nutrient metabolic variation in alfalfa leaves at different growth stages have been clearly reported. We have used correlation and network analyses of the alfalfa leaf metabolome, proteome, and transcriptome to explore chlorophyll, flavonoid, and amino acid content at two development stages: budding stage (BS) and full-bloom stage (FBS). A high correlation between the expression of biosynthetic genes and their metabolites revealed significant reductions in metabolite content as the plant matured from BS to FBS. l-Glutamate, the first molecule of chlorophyll biosynthesis, decreased, and the expression of HemA, which controls the transformation of glutamyl-tRNA to glutamate 1-semialdehyde, was down-regulated, leading to a reduction in leaf chlorophyll content. Flavonoids also decreased, driven at least in part by increased expression of the gene encoding CYP75B1: flavonoid 3'-monooxygenase, which catalyzes the hydroxylation of dihydroflavonols and flavonols, resulting in degradation of flavonoids. Expression of NITRILASE 2 (NIT2) and Methyltransferase B (metB), which regulate amino acid metabolism and influence the expression of genes of the glycolysis-TCA pathway, were down-regulated, causing amino acid content in alfalfa leaves to decrease at FBS. This study provides new insights into the complex regulatory network governing the content and decrease of chlorophyll, amino acids, flavonoids, and other nutrients in alfalfa leaves during maturation. These results further provide a theoretical basis for the generation of alfalfa varieties exhibiting higher nutritional quality, high-yield cultivation, and a timely harvest.

Pea-Tea Intercropping Improves Tea Quality through Regulating Amino Acid Metabolism and Flavonoid Biosynthesis.

Pea-tea intercropping is an excellent cultivation method that can improve tea quality. However, the underlying mechanism is still unclear. The present study was aimed at elucidating the mechanism of the effect of pea-tea intercropping on tea quality through a high-throughput method. Transcriptome and metabolome analyses were conducted to identify the changes in gene expression and metabolites changes intercropping, respectively. In addition, the amino acids and catechins were detected using the LC-MS method and quantified absolutely. The results showed that total polyphenols and catechins decreased but amino acids increased in pea intercropped tea shoots. Correspondingly, genes related to amino acid metabolism and flavonoid biosynthesis were differentially expressed. For amino acid metabolism, 11 differentially expressed genes were identified, including 5 upregulated and 6 downregulated genes. Meanwhile, three genes involved in carbohydrate transport and metabolism were upregulated in pea intercropped tea plants. These genes were also involved in amino acid metabolism. For flavonoid biosynthesis, two downregulated genes were identified, which were the flavonol synthase and anthocyanidin synthase genes and followed a similar pattern to changes in catechins and polyphenols. These advances have opened new horizons for understanding the biochemical mechanisms of amino acids and flavonoids in improving tea quality in the pea-tea intercropping cultivation model.

Effect of Lactobacillus rhamnosus hsryfm 1301 Fermented Milk on Lipid Metabolism Disorders in High-Fat-Diet Rats.

To further explore and improve the mechanism of probiotics to alleviate the disorder of lipid metabolism, transcriptomic and metabolomic with bioinformatic analysis were combined. In the present study, we successfully established a rat model of lipid metabolism disorder using a high-fat diet. Intervention with Lactobacillus rhamnosus hsryfm 1301 fermented milk resulted in a significant reduction in body weight, serum free fatty acid and blood lipid levels (p &lt; 0.05), which predicted that the lipid metabolism disorder was alleviated in rats. Metabolomics and transcriptomics identified a total of 33 significantly different metabolites and 183 significantly different genes screened in the intervention group compared to the model group. Comparative analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations identified a total of 61 pathways in which differential metabolites and genes were jointly involved, with linoleic acid metabolism, glycine, serine and threonine metabolism and glutamatergic synapse in both transcriptome and metabolome being found to be significantly altered (p &lt; 0.05). Lactobacillus rhamnosus hsryfm 1301 fermented milk was able to directly regulate lipid metabolism disorders by regulating the metabolic pathways of linoleic acid metabolism, glycerophospholipid metabolism, fatty acid biosynthesis, alpha-linolenic acid metabolism, fatty acid degradation, glycerolipid metabolism and arachidonic acid metabolism. In addition, we found that Lactobacillus rhamnosus hsryfm 1301 fermented milk indirectly regulates lipid metabolism through regulating amino acid metabolism, the nervous system, the endocrine system and other pathways. Lactobacillus rhamnosus hsryfm 1301 fermented milk could alleviate the disorders of lipid metabolism caused by high-fat diet through multi-target synergy.

D-mannose alleviated alveolar bone loss in mice with experimental periodontitis via regulating the anti-inflammatory effect of amino acids.

Periodontitis is a chronic infectious disease caused by dysbiosis of oral microbiota, ultimately leading to periodontal alveolar bone loss. The oral subgingival microbiome, a key role in periodontitis pathogenesis, could alter the composition of gut microbiomes resulting in intestinal microbiota disorder. D-mannose plays an important role in glucose metabolism; whether it is beneficial to prevention and treatment of periodontitis and the regulation of oral and intestinal microbiota changes is still unknown. To explore the effect of D-mannose, we established experimental periodontitis models in mice and then treated with supplementation of D-mannose in drinking water or gavage to examine the extent of periodontal bone loss using methylene blue staining. Moreover, the oral and fecal samples of mice were collected for 16S rRNA deep sequencing to analyze the changes of oral and gut microbiota after 14 days. Furthermore, amino acid content assays were used to test the concentration of amino acid of gingival tissues and intestinal tissues. We found that D-mannose could alleviate periodontal bone loss whether in the manner of drinking water or gavage. 16S rRNA results revealed that the abundance of Firmicutes changed significantly in oral samples, while Firmicutes and Akkermansia muciniphila were dominated in gut microbiota. In addition, we demonstrated that D-mannose inhibited inflammation and alleviated alveolar bone loss in periodontitis via regulating amino acid metabolism of oral and gut microbiomes. Our findings provided insight into the mechanism underlying the abilities of D-mannose in improving periodontitis treatment, suggesting that D-mannose has potential application in the dental clinic.

Anthocyanin improves kidney function in diabetic kidney disease by regulating amino acid metabolism

BackgroundDiabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways.MethodsTo explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis.ResultsWe showed that the fasting blood glucose level (− 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (− 24.1 μm, P = 0.030), fibrosis score of glomerular (− 8.8%, P = 0.002), and kidney function (Cystatin C: − 701.4 pg/mL, P = 0.043; urine creatinine: − 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating.ConclusionsOur results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD.

Uridine affects amino acid metabolism in sow-piglets model and increases viability of pTr2 cells.

As an important nucleoside precursor in salvage synthesis pathway of uridine monophosphate, uridine (UR) is the most abundant nucleotide in sow milk. This study aimed to investigate the effects of maternal UR supplementation during second trimester of gestation on reproductive performance and amino acid metabolism of Sows. Results showed that compared to CON group, the average number of stillborn piglets per litter was significantly reduced (P < 0.05) with higher average piglet weight at birth in UR group (P = 0.083). Besides, dietary UR supplementation significantly increased TP in sow serum, BUN content in cord serum, and TP and ALB in newborn piglet serum (P < 0.05); but decreased AST level in sow serum and BUN level in piglet serum (P < 0.05). Importantly, free amino acids profile in sow serum newborn piglet serum and colostrum was changed by maternal UR supplementation during day 60 of pregnancy, as well as the expression of amino acids transporter (P < 0.05). In addition, from 100 to 2,000 μM UR can increased the viability of pTr2 cells. The UR exhibited higher distribution of G1/M phase of cell cycle at 400 μM compared with 0 μM, and reduced S-phases of cell cycle compared with 0 and 100μM (P < 0.05). Supplementation of uridine during day 60 of pregnancy can improve reproductive performance, regulate amino acid metabolism of sows and their offspring, and increase the viability of pTr2 cells.

Insights into the roles and driving forces of CCT3 in human tumors.

CCT3 played a key role in many cancers. This study aimed to further explore the characteristics of CCT3 from a pan-cancer perspective and reveal the driving forces for CCT3. By bioinformatic analysis, we found that the mRNA and protein levels of CCT3 were abnormally elevated in most tumor types and were correlated with poor prognosis. Single-cell sequencing data indicated an abnormal increase of CCT3 expression in both malignant cells and multiple immune cells. In the tumor microenvironment, CCT3 expression was negatively relevant with immune cell infiltration and immune checkpoint genes expression. In colon cancer, knockdown of CCT3 inhibited cell proliferation. Gene set enrichment analysis showed that CCT3 may be oncogenic by regulating amino acid metabolism. Furthermore, we predicted sensitive drugs for CCT3 by virtual screening and sensitivity analysis. Many driver genes such as TP53 and KRAS were essential for CCT3 overexpression. Epigenetic factors, enhancers in particular, were also critical for CCT3 expression. Additionally, we constructed the lncRNA/circRNA-miRNA-CCT3 regulatory network. Collectively, CCT3 had the potential to be a diagnostic and prognostic biomarker for multiple tumor types. CCT3 expression was relevant with an immunosuppressive tumor microenvironment. CCT3 could be a new molecular target for colon cancer. Both genetic and epigenetic factors were responsible for CCT3 expression in tumors.