PubMed

Int J Mol Sci. 2023 Jun 9;24(12):9949. doi: 10.3390/ijms24129949.ABSTRACTThe high adaptability of insects to food sources has contributed to their ranking among the most abundant and diverse species on Earth. However, the molecular mechanisms underlying the rapid adaptation of insects to different foods remain unclear. We explored the changes in gene expression and metabolic composition of the Malpighian tubules as an important metabolic excretion and detoxification organ in silkworms (Bombyx mori) fed mulberry leaf and artificial diets. A total of 2436 differentially expressed genes (DEGs) and 245 differential metabolites were identified between groups, with the majority of DEGs associated with metabolic detoxification, transmembrane transport, and mitochondrial function. Detoxification enzymes, such as cytochrome P450 (CYP), glutathione-S-transferase (GST), and UDP-glycosyltransferase, and ABC and SLC transporters of endogenous and exogenous solutes were more abundant in the artificial diet group. Enzyme activity assays confirmed increased CYP and GST activity in the Malpighian tubules of the artificial diet-fed group. Metabolome analysis showed increased contents of secondary metabolites, terpenoids, flavonoids, alkaloids, organic acids, lipids, and food additives in the artificial diet group. Our findings highlight the important role of the Malpighian tubules in adaptation to different foods and provide guidance for further optimization of artificial diets to improve silkworm breeding.PMID:37373097 | DOI:10.3390/ijms24129949

Int J Mol Sci. 2023 Jun 7;24(12):9839. doi: 10.3390/ijms24129839.ABSTRACTGalls have become the best model for exploring plant-gall inducer relationships, with most studies focusing on gall-inducing insects but few on gall mites. The gall mite Aceria pallida is a major pest of wolfberry, usually inducing galls on its leaves. For a better understanding of gall mite growth and development, the dynamics of the morphological and molecular characteristics and phytohormones of galls induced by A. pallida were studied by histological observation, transcriptomics and metabolomics. The galls developed from cell elongation of the epidermis and cell hyperplasia of mesophylls. The galls grew quickly, within 9 days, and the mite population increased rapidly within 18 days. The genes involved in chlorophyll biosynthesis, photosynthesis and phytohormone synthesis were significantly downregulated in galled tissues, but the genes associated with mitochondrial energy metabolism, transmembrane transport, carbohydrates and amino acid synthesis were distinctly upregulated. The levels of carbohydrates, amino acids and their derivatives, and indole-3-acetic acid (IAA) and cytokinins (CKs), were markedly enhanced in galled tissues. Interestingly, much higher contents of IAA and CKs were detected in gall mites than in plant tissues. These results suggest that galls act as nutrient sinks and favor increased accumulation of nutrients for mites, and that gall mites may contribute IAA and CKs during gall formation.PMID:37372986 | DOI:10.3390/ijms24129839

Int J Mol Sci. 2023 Jun 7;24(12):9832. doi: 10.3390/ijms24129832.ABSTRACTSystemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and, when dysregulated, may cause serious complications. Losartan (LOS) blocks relevant physiological aspects of hypertension, acting mainly on the reduction of peripheral vascular resistance. Complications of hypertension include nephropathy, in which diagnosis is based on the observation of functional or structural renal dysfunction. Therefore, blood pressure control is essential to attenuate the progression of chronic kidney disease (CKD). In this study, 1H NMR metabolomics were used to differentiate hypertensive and chronic renal patients. Plasmatic levels of LOS and EXP3174, obtained by liquid chromatography coupled with mass-mass spectroscopy, were correlated with blood pressure control, biochemical markers and the metabolomic fingerprint of the groups. Some biomarkers have been correlated with key aspects of hypertension and CKD progression. For instance, higher levels of trigonelline, urea and fumaric acid were found as characteristic markers of kidney failure. In the hypertensive group, the urea levels found could indicate the onset of kidney damage when associated with uncontrolled blood pressure. In this sense, the results point to a new approach to identify CKD in early stages and may contribute to improving pharmacotherapy and reducing morbidity and mortality associated with hypertension and CKD.PMID:37372980 | DOI:10.3390/ijms24129832

Int J Mol Sci. 2023 Jun 6;24(12):9789. doi: 10.3390/ijms24129789.ABSTRACTThis study investigated the importance of a metabolomic analysis in a complex disease such as nonalcoholic steatohepatitis (NASH) associated with obesity. Using an untargeted metabolomics technique, we studied blood metabolites in 216 morbidly obese women with liver histological diagnosis. A total of 172 patients were diagnosed with nonalcoholic fatty liver disease (NAFLD), and 44 were diagnosed with normal liver (NL). Patients with NAFLD were classified into simple steatosis (n = 66) and NASH (n = 106) categories. A comparative analysis of metabolites levels between NASH and NL demonstrated significant differences in lipid metabolites and derivatives, mainly from the phospholipid group. In NASH, there were increased levels of several phosphatidylinositols and phosphatidylethanolamines, as well as isolated metabolites such as diacylglycerol 34:1, lyso-phosphatidylethanolamine 20:3 and sphingomyelin 38:1. By contrast, there were decreased levels of acylcarnitines, sphingomyelins and linoleic acid. These findings may facilitate identification studies of the main pathogenic metabolic pathways related to NASH and may also have a possible applicability in a panel of metabolites to be used as biomarkers in future algorithms of the disease diagnosis and its follow-up. Further confirmatory studies in groups with different ages and sexes are necessary.PMID:37372937 | DOI:10.3390/ijms24129789

Foods. 2023 Jun 20;12(12):2430. doi: 10.3390/foods12122430.ABSTRACTIn this study, the effects of different sun withering degrees (75% (CK), 69% (S69), 66% (S66), 63% (S63), and 60% (S60) water content in the withered leaves) on black tea sensory quality were investigated by means of sensory evaluation plus metabolomics analysis. Sensory evaluation results showed higher sensory quality scores for the black tea in S69-S66, due to better freshness, sweeter taste, and a sweet and even floral and fruity aroma. Additionally, 65 non-volatile components were identified using Ultra Performance Liquid Chromatography-Quadrupole-Time of Flight-Mass Spectrometry (UPLC-Q-TOF/MS). Among them, the content increase of amino acids and theaflavins was found to promote the freshness and sweetness of black tea. The aroma of tea was analyzed using combined Solvent Assisted Flavor Evaporation-Gas Chromatography-Mass Spectrometry (SAFE-GC-MS) and Headspace-Solid Phase Micro Extract-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS), and 180 volatiles were identified, including 38 variable importance in projection (VIP) > 1 (p < 0.05) and 25 Odor Activity Value (OAV) > 1 volatiles. Statistical analysis revealed 11 volatiles as potential major aroma differential metabolites in black tea with a different sun withering degree, such as volatile terpenoids (linalool, geraniol, (E)-citral, and β-myrcene), amino-acid-derived volatiles (benzeneethanol, benzeneacetaldehyde, and methyl salicylate), carotenoid-derived volatiles (jasmone and β-damascenone), and fatty-acid-derived volatiles ((Z)-3-hexen-1-ol and (E)-2-hexenal). Among them, volatile terpenoids and amino acid derived volatiles mainly contributed to the floral and fruity aroma quality of sun-withered black tea.PMID:37372642 | DOI:10.3390/foods12122430

Foods. 2023 Jun 18;12(12):2407. doi: 10.3390/foods12122407.ABSTRACTTo enrich the flavor compounds and retain the content of polyphenolics in grape juice (GJ) under long-term storage, Lactiplantibacillus plantarum, Lactobacillus acidophilus, Lacticaseibacillus casei, and Lacticaseibacillus paracasei, were screened and the optimal fermentation conditions were determined as fermentation temperature of 41.2 °C for 24 h with an initial LAB density of 8.5 × 106 CFU/mL. Surprisingly, the retention rates of TPC still remained at 50% after storage for 45 days at 4 °C. Moreover, 251 different metabolites were identified, include 23 polyphenolics, 11 saccharides, and 9 organic acids. Most importantly, the total content of polyphenolics reserved was 92.65% at the end of fermentation. Among them, ephedrannin A content significantly decreased; however, 2',6'-Di-O-acetylononin gradually increased with the fermentation time, which resulted in FGJ maintaining excellent bioactivity. Meanwhile, organic acid content (palmitoylethanolamide, tetraacetylethylenediamine) increased with saccharides (linamarin) decreasing, which leads to FGJ having a unique taste. Furthermore, a total of 85 Volatile organic compounds (VOCs) were identified, mainly including esters, aldehydes, and alcohols. Interestingly, key VOCs could be formed by carboxylic acids and derivatives, and fatty acyls via complex metabolic pathways.PMID:37372618 | DOI:10.3390/foods12122407

Foods. 2023 Jun 18;12(12):2404. doi: 10.3390/foods12122404.ABSTRACTStingless bee honey (SBH) is a natural, sweet product produced by stingless bees (Meliponini tribe) that has been used as a traditional medicine to treat various illnesses. It has been shown that SBH has high nutritional value and health-promoting properties due to the presence of plant bioactive compounds from different botanical flora of the foraged nectar. In this study, the antioxidant activities of seven monofloral honeys from acacia, agarwood, coconut, dwarf mountain pine (DMP), Mexican creeper (MC), rubber, and starfruit botanical origins were investigated. The antioxidant properties of SBH studied had a range from 19.7 to 31.4 mM TE/mg for DPPH assays, 16.1 to 29.9 mM TE/mg for ABTS assays, 69.0 to 167.6 mM TE/mg for ORAC assays, and 45.5 to 89.3 mM Fe2+/mg for FRAP assays. Acacia honey showed the highest level of antioxidant properties. The models built from mass spectral fingerprints from direct ambient mass spectrometry showed distinct clusters of SBH by botanical origin and correlated with the antioxidant properties. An untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach was undertaken to identify the antioxidant compounds that could explain the unique antioxidant and compositional profiles of the monofloral SBH by its botanical origin. The antioxidants that were identified predominantly consisted of alkaloids and flavonoids. Flavonoid derivatives, which are potent antioxidants, were found to be key markers of acacia honey. This work provides the fundamental basis for the identification of potential antioxidant markers in SBH associated with the botanical origin of the foraged nectar.PMID:37372615 | DOI:10.3390/foods12122404

Foods. 2023 Jun 15;12(12):2377. doi: 10.3390/foods12122377.ABSTRACTPanax notoginseng (P. notoginseng) has excellent medicinal and food dual-use characteristics. However, P. notoginseng with a unique origin label has become the target of fraud because of people confusing or hiding its origin. In this study, an untargeted nuclear magnetic resonance (NMR)-based metabolomics approach was used to discriminate the geographical origins of P. notoginseng from four major producing areas in China. Fifty-two components, including various saccharides, amino acids, saponins, organic acids, and alcohols, were identified and quantified through the NMR spectrum, and the area-specific geographical identification components were further screened. P. notoginseng from Yunnan had strong hypoglycemic and cardiovascular protective effects due to its high acetic acid, dopamine, and serine content, while P. notoginseng from Sichuan was more beneficial for diseases of the nervous system because of its high content of fumarate. P. notoginseng from Guizhou and Tibet had high contents of malic acid, notoginsenoside R1, and amino acids. Our results can help to distinguish the geographical origin of P. notoginseng and are readily available for nutritional recommendations in human consumption.PMID:37372587 | DOI:10.3390/foods12122377

Foods. 2023 Jun 9;12(12):2331. doi: 10.3390/foods12122331.ABSTRACTAcheta domesticus (house cricket) has been recently introduced into the official European list of novel foods, representing an alternative and sustainable food source. Up to now, the chemical characterization of this edible insect has been focused only on specific classes of compounds. Here, three production batches of an A. domesticus powder were investigated by means of a multimethodological approach based on NMR, FT-ICR MS, and GC-MS methodologies. The applied analytical protocol, proposed for the first time in the study of an edible insect, allowed us to identify and quantify compounds not previously reported in crickets. In particular, methyl-branched hydrocarbons, previously identified in other insects, together with other compounds such as citrulline, formate, γ-terpinene, p-cymene, α-thujene, β-thujene, and 4-carene were detected. Amino acids, organic acids, and fatty acids were also identified and quantified. The improved knowledge of the chemical profile of this novel food opens new horizons both for the use of crickets as a food ingredient and for the use of extracts for the production of new formulations. In order to achieve this objective, studies regarding safety, biological activity, bioaccessibility, and bioavailability are needed as future perspectives in this field.PMID:37372542 | DOI:10.3390/foods12122331

Foods. 2023 Jun 7;12(12):2297. doi: 10.3390/foods12122297.ABSTRACTAnthocyanins are important secondary metabolites in fruits, and anthocyanin accumulation in the flesh of peach exhibits a spatial pattern, but the relevant mechanism is still unknown. In this study, the yellow-fleshed peach, cv. 'Jinxiu', with anthocyanin accumulation in the mesocarp around the stone was used as the experimental material. Red flesh (RF) and yellow flesh (YF) were sampled separately for flavonoid metabolite (mainly anthocyanins), plant hormone, and transcriptome analyses. The results showed that the red coloration in the mesocarp was due to the accumulation of cyanidin-3-O-glucoside, with an up-regulation of anthocyanin biosynthetic genes (F3H, F3'H, DFR, and ANS), transportation gene GST, and regulatory genes (MYB10.1 and bHLH3). Eleven ERFs, nine WRKYs, and eight NACs were also defined as the candidate regulators of anthocyanin biosynthesis in peach via RNA-seq. Auxin, cytokinin, abscisic acid (ABA), salicylic acid (SA), and 1-aminocyclopropane-1-carboxylic acid (ACC, ethylene precursor) were enriched in the peach flesh, with auxin, cytokinin, ACC, and SA being highly accumulated in the RF, but ABA was mainly distributed in the YF. The activators and repressors in the auxin and cytokinin signaling transduction pathways were mostly up-regulated and down-regulated, respectively. Our results provide new insights into the regulation of spatial accumulation pattern of anthocyanins in peach flesh.PMID:37372513 | DOI:10.3390/foods12122297

Foods. 2023 Jun 7;12(12):2294. doi: 10.3390/foods12122294.ABSTRACTProso millet (Panicum miliaceum) is neglected in human nutrition. Thanks to the composition of the grains, millet is suitable for people with celiac disease and it is also useful in the prevention of cardiovascular diseases. For screening the substances in all plant parts of millet via GC-MS, two varieties, Hanacká Mana and Unicum, were used. Substances from the group saccharides, amino acids, fatty acids, carboxylic acids, phytosterols and others were identified in the roots, leaves, stems, and seeds. The highest level of saccharides was found in the stems (83%); amino acids in the roots (6.9%); fatty acids in the seeds (24.6%); carboxylic acids in the roots (3%), phytosterols in the seeds (10.51%); other substances, such as tetramethyl-2-hexadecenol (1.84%) and tocopherols (2.15%), in the leaves; retinal in the roots (1.30%) and squalene in the seeds (1.29%). Saccharides were the dominant group in all plant parts of proso millet followed by fatty acids. The dominant saccharides in all parts of the millet plant were sucrose, fructose and psicose. On the contrary, turanose, trehalose, glucose and cellobiose belonged to the least represented sugars. Additionally, amyrin, miliacin, campesterol, stigmasterol, β-sitosterol, and others were identified. Varietal variability can be assumed, e.g., in retinal, miliacin or amyrin content.PMID:37372504 | DOI:10.3390/foods12122294

Genes (Basel). 2023 Jun 19;14(6):1290. doi: 10.3390/genes14061290.ABSTRACTAs the main reserve carbohydrate in garlic, fructan contributes to garlic's yield and quality formation. Numerous studies have shown that plant fructan metabolism induces a stress response to adverse environments. However, the transcriptional regulation mechanism of garlic fructan in low-temperature environments is still unknown. In this study, the fructan metabolism of garlic seedlings under low-temperature stress was revealed by transcriptome and metabolome approaches. With the extension of stress time, the number of differentially expressed genes and metabolites increased. Using weighted gene co-expression network analysis (WGCNA), three key enzyme genes related to fructan metabolism were screened (a total of 12 transcripts): sucrose: sucrose 1-fructosyltransferase (1-SST) gene; fructan: fructan 6G fructosyltransferase (6G-FFT) gene; and fructan 1-exohydrolase (1-FEH) gene. Finally, two hub genes were obtained, namely Cluster-4573.161559 (6G-FFT) and Cluster-4573.153574 (1-FEH). The correlation network and metabolic heat map analysis between fructan genes and carbohydrate metabolites indicate that the expression of key enzyme genes in fructan metabolism plays a positive promoting role in the fructan response to low temperatures in garlic. The number of genes associated with the key enzyme of fructan metabolism in trehalose 6-phosphate was the highest, and the accumulation of trehalose 6-phosphate content may mainly depend on the key enzyme genes of fructan metabolism rather than the enzyme genes in its own synthesis pathway. This study not only obtained the key genes of fructan metabolism in garlic seedlings responding to low temperatures but also preliminarily analyzed its regulatory mechanism, providing an important theoretical basis for further elucidating the cold resistance mechanism of garlic fructan metabolism.PMID:37372470 | DOI:10.3390/genes14061290

Front Biosci (Elite Ed). 2023 Apr 4;15(2):8. doi: 10.31083/j.fbe1502008.ABSTRACTBACKGROUND: Chronic kidney disease (CKD) is a common condition in cats and cachexia (loss of lean body mass) is a concern. A nutrition-based intervention was investigated in cats with CKD for its effects on body composition, the plasma metabolome, and possible implications on health.METHODS: After a 4-week prefeed period with the control food, cats with CKD (N = 24) were randomized to one of six groups to consume a control food; a food supplemented with 0.5% betaine, 0.39% oat beta-glucan, and 0.27% short-chain fructooligosaccharides (scFOS, test food 1); and a food supplemented with 0.5% betaine, 0.59% oat beta-glucan, and 0.41% scFOS (test food 2) in a William's Latin Square design, each for 10 weeks. Body composition was assessed via dual-energy X-ray absorptiometry measurements, and the plasma metabolome was characterized.RESULTS: Despite no significant differences in daily intake among the three foods, significant increases in total body mass, lean body mass, and lean plus bone mineral composition were observed when cats with CKD consumed test food 1 compared with the control food; numerical increases were seen with test food 2 versus the control food. Plasma metabolomics indicated increased one-carbon metabolism following consumption of test food 1 and/or 2, with significant increases in sarcosine and numerical increases in methionine. Lower levels of plasma trans-4-hydroxyproline and N-methylproline following consumption of test foods 1 and 2 indicates reduced collagen breakdown and perhaps reduced fibrosis. Several acylcarnitines and branched-chain fatty acids associated with CKD were also reduced when cats ate test food 1 or 2 versus the control food. Higher plasma levels of sphingomyelins with consumption of test food 1 or 2 may reflect less severe CKD.CONCLUSIONS: Consumption of foods with supplemental betaine and fibers by cats with CKD led to improvements in body composition and changes in the plasma metabolome that correspond to better kidney health.PMID:37369569 | DOI:10.31083/j.fbe1502008

BMJ Open Diabetes Res Care. 2023 Jun;11(3):e003327. doi: 10.1136/bmjdrc-2023-003327.ABSTRACTINTRODUCTION: Hypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes.RESEARCH DESIGN AND METHODS: Twenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.RESULTS: In total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10-3) and isoleucine (p=2.2×10-3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days.CONCLUSIONS: In individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations.TRIAL REGISTRATION NUMBER: NCT01337362.PMID:37369531 | DOI:10.1136/bmjdrc-2023-003327

Spine J. 2023 Jun 25:S1529-9430(23)03238-2. doi: 10.1016/j.spinee.2023.06.396. Online ahead of print.ABSTRACTBACKGROUND: The majority of literature on bacterial flora in the disc stands disadvantaged in utilizing traditional culture methods and targeting a single bacterium, Cutibacterium acnes.OBJECTIVE: Our objective was to document the diversity in the bacterial flora between normal and degenerated discs for shortlisting potential pathogens using next-generation genomic tools.STUDY DESIGN: Experimental case-control study METHODS: 16S metagenome sequencing was employed to profile bacterial diversity in MRI normal healthy discs from brain-dead organ voluntary donors (n=20) and 40 degenerated disc samples harvested during surgery (Modic (MC)= 20 and Non-Modic (NMC) = 20). The V3-V4 region was amplified using universal bacterial primers 341F and 806R, and the libraries were sequenced using ILUMINA NOVOSEQ 6000 platform. Statistical significance was set at Bacteria with a minimum of 100 OTU (Operational Taxonomic Unit) and present in at least 70% of the samples. The QC-filtered reads were processed using the QIIME-2 pipeline. The OTU clustering and taxonomic classification were carried out for the merged reads using the Greengenes/SILVA reference database. Validation was done by identification of bacterial metabolites in samples using the LC-MS/MS approach.RESULTS: Abundant bacteria differing widely in diversity, as evidenced by Alpha and Beta diversity analysis, were present in all control and degenerative samples. The number of bacterial genera was 27 (14- gram-positive: 13- gram-negative) in the control group, 23 (10- gram-positive: 11- gram-negative) in the Modic group, and 16 (11- gram-positive: 5- gram-negative) in the non-Modic group. In the Modic group, Gram-negative bacteria OTUs were found to be predominant (more than 50% of the total bacteria identified), whereas in control and non-Modic groups the OTUs of gram-positive bacteria were predominant. Species-level analysis revealed an abundance of opportunistic gram-negative pathogens like Pseudomonas aeruginosa, Sphingomonos paucibacillus, and Ochrobactrum quorumnocens in the discs with Modic changes, more than in non-Modic discs. The presence of bacterial metabolites and quorum-sensing molecules like N-decanoyl-L-homoserine lactone, 6-Hydroxynicotinic acid, 2-Aminoacetophenone, 4-Hydroxy-3-polyprenylbenzoate, PE (16:1(9Z)/18:0) and Phthalic acid validated the colonization and cell-cell communication of bacteria in disc ruling out contamination theory. C. acnes was not the predominant bacteria in any of the three groups of discs and in fact was in the 16th position in the order of abundance in the control discs (0.72%), 7th position in the Modic discs (1.41%), and 12th position (0.53%) in the non-Modic discs.CONCLUSION: This study identified a predominance of gram-negative bacteria in degenerated discs and highlights that C. acnes may not be the only degeneration-causing bacteria. This may be attributed to the environment, diet, and lifestyle habits of the sample population. Though the study does not reveal the exact pathogen, it may pave the way for future studies on the subject.CLINICAL SIGNIFICANCE: These findings invite further investigation into causal relationships of bacterial profile with disc degeneration phenotypes as well as phenotype-driven clinical treatment protocols.PMID:37369253 | DOI:10.1016/j.spinee.2023.06.396

Gynecol Endocrinol. 2023 Dec;39(1):2227276. doi: 10.1080/09513590.2023.2227276.NO ABSTRACTPMID:37369250 | DOI:10.1080/09513590.2023.2227276

Microbiome. 2023 Jun 28;11(1):144. doi: 10.1186/s40168-023-01573-3.ABSTRACTBACKGROUND: Marine prokaryotes are a rich source of novel bioactive secondary metabolites for drug discovery. Recent genome mining studies have revealed their great potential to bio-synthesize novel secondary metabolites. However, the exact biosynthetic chemical space encoded by the marine prokaryotes has yet to be systematically evaluated.RESULTS: We first investigated the secondary metabolic potential of marine prokaryotes by analyzing the diversity and novelty of the biosynthetic gene clusters (BGCs) in 7541 prokaryotic genomes from cultivated and single cells, along with 26,363 newly assembled medium-to-high-quality genomes from marine environmental samples. To quantitatively evaluate the unexplored biosynthetic chemical space of marine prokaryotes, the clustering thresholds for constructing the biosynthetic gene cluster and molecular networks were optimized to reach a similar level of the chemical similarity between the gene cluster family (GCF)-encoded metabolites and molecular family (MF) scaffolds using the MIBiG database. The global genome mining analysis demonstrated that the predicted 70,011 BGCs were organized into 24,536 mostly new (99.5%) GCFs, while the reported marine prokaryotic natural products were only classified into 778 MFs at the optimized clustering thresholds. The number of MF scaffolds is only 3.2% of the number of GCF-encoded scaffolds, suggesting that at least 96.8% of the secondary metabolic potential in marine prokaryotes is untapped. The unexplored biosynthetic chemical space of marine prokaryotes was illustrated by the 88 potential novel antimicrobial peptides encoded by ribosomally synthesized and post-translationally modified peptide BGCs. Furthermore, a sea-water-derived Aquimarina strain was selected to illustrate the diverse biosynthetic chemical space through untargeted metabolomics and genomics approaches, which identified the potential biosynthetic pathways of a group of novel polyketides and two known compounds (didemnilactone B and macrolactin A 15-ketone).CONCLUSIONS: The present bioinformatics and cheminformatics analyses highlight the promising potential to explore the biosynthetic chemical diversity of marine prokaryotes and provide valuable knowledge for the targeted discovery and biosynthesis of novel marine prokaryotic natural products. Video Abstract.PMID:37370187 | DOI:10.1186/s40168-023-01573-3

J Exp Clin Cancer Res. 2023 Jun 28;42(1):155. doi: 10.1186/s13046-023-02698-x.ABSTRACTBACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) tends to undergo distant metastasis, especially liver metastasis, leading to a poor prognosis. Metabolic remodelling and epigenetic reprogramming are two important hallmarks of malignant tumours and participate in regulating PDAC tumorigenesis and metastasis. However, the interaction between these two processes during PDAC metastasis has not been fully elucidated.METHODS: We performed metabolomics analysis to identify the critical metabolites associated with PDAC liver metastasis and focused on guanidinoacetic acid (GAA). Intracellular GAA content was significantly increased in liver metastatic PDAC cells compared to primary cancer cells in mouse xenograft tumour models. The effects of GAA supplementation and glycine amidinotransferase (GATM) knockdown on PDAC metastasis were assessed by analysing cell migration, filopodia formation, epithelial-mesenchymal transition (EMT), and in vivo metastasis in different cell and animal models. Next, ChIP‒qPCR, 3C‒qPCR, and CRISPRi/dCas9-KRAB experiments were used to validate the "epigenome-metabolome" mechanism. Finally, the results of in vitro approaches, including RNA-seq, CUT&RUN, RT‒qPCR, and western blot analyses, as well as luciferase reporter gene assay and transwell assay, revealed the GAA-c-Myc-HMGA axis and transcription-activating histone modifications reprogramming.RESULTS: A high level of intracellular GAA was associated with PDAC liver metastasis. GAA could promote the migration, EMT, and liver metastasis of pancreatic cancer cells in vitro and in vivo. Next, we explored the role of GATM-mediated de novo GAA synthesis in pancreatic cancer metastasis. High expression of GATM was positively correlated with advanced N stage in PDAC. Knockdown of GATM significantly reduced the intracellular level of GAA, suppressed EMT, and inhibited PDAC liver metastasis, and these effects were attenuated by GAA supplementation. Mechanistically, we identified the active enhancers looped to the Gatm gene locus that promoted GATM expression and PDAC liver metastasis. Furthermore, we found that GAA promoted cell migration and EMT by regulating c-Myc-mediated high mobility group AT-hook protein expression. Moreover, GAA increased the H3K4me3 modification level by upregulating histone methyltransferases, which induced the transcription of metastasis-related genes, including Myc.CONCLUSIONS: These findings revealed the critical role of the epigenome-metabolome interaction in regulating PDAC liver metastasis and suggested potential therapeutic strategies targeting GAA metabolism and epigenetic regulatory mechanisms.PMID:37370109 | DOI:10.1186/s13046-023-02698-x

BMC Complement Med Ther. 2023 Jun 27;23(1):212. doi: 10.1186/s12906-023-04043-3.ABSTRACTBACKGROUND: Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms.METHODS: Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Ι and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA).RESULTS: CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD + levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Ι inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Ι were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Ι.CONCLUSION: Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Ι.PMID:37370057 | DOI:10.1186/s12906-023-04043-3

World J Microbiol Biotechnol. 2023 Jun 28;39(9):236. doi: 10.1007/s11274-023-03680-7.ABSTRACTIncreased attention has been given to whole grain and plant-based foods due to health concerns. Sweet fermented oats (SFOs) are such traditional fermented food from China. However, reports on their microbiota and relations with the nutrients and flavor were scarcely few, hindering their wider application. The comprehensive microbial composition, metabolic compounds and their correlations of representative SFOs from northwestern China were firstly investigated. Firmicutes predominated the microbial communities, followed by Proteobacteria. Weissella, Bacillus and Lactobacillus were dominant bacterial genera, biomarkers and core bacteria as well. GC-MS (Gas Chromatography-Mass Spectrometer) identified the metabolic compounds, among which the categories fatty acids and carboxylic acids most abundant. Eighteen chemicals showed significant differences among the five SFOs, including ethyl octanoate, neryl acetate, L-sorbose, diglycerol, cellotetraose etc. Fatty acids, carboxylic acids, amino acids, peptides, oligosaccharides, and monosaccharides were the key substances responsible for the unique flavor and rich nutrients in SFOs. The core bacteria were closely related to chemical acids, esters, flavone and alcohol. Pediococcus showed a negative correlation with 2,3-butanediol. SFOs were made in the laboratory with the core bacterial strains, obtaining a high abundance of nutrient chemicals and sensory evaluation value. The research provided a foundation for the improvement, further application and industrialization of SFOs.PMID:37369859 | DOI:10.1007/s11274-023-03680-7