PubMed

Plants (Basel). 2024 Jun 16;13(12):1665. doi: 10.3390/plants13121665.ABSTRACTWith the internationalization of Chinese culture, ready-to-cook Chinese food has become popular. Vegetables in Chinese preparations are usually cut into slices, cubes, and shreds. Carrots, as a typical Chinese side dish, were selected as the model in this work. The polyphenol content, antioxidant capacity, O2-, hydrogen peroxide, malondialdehyde, lignin, antioxidant enzymes, and other enzymes activities were analyzed. The results indicated that these parameters were insignificantly different between three cutting styles. Therefore, metabolomics is further employed. Pathway enrichment indicated that glyceollin II and 6″-malonylgenistin were metabolites particularly expressed in the isoflavonoid biosynthesis pathway; (+)-gallocatechin, trans-chlorogenic acid, and (-)-epiafzelechin were specifically identified in the flavonoid biosynthesis pathway after slicing; and shredding caused the expression of coniferyl aldehyde and eugenol, which were specifically expressed in the phenylpropanoid biosynthesis pathway. These results indicate that different cutting styles do not change the physiological indicators of carrots but induce the expression of specific metabolites.PMID:38931097 | DOI:10.3390/plants13121665

Plants (Basel). 2024 Jun 12;13(12):1627. doi: 10.3390/plants13121627.ABSTRACTPhlomoides rotata is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of the P. rotata used as medical ingredients and display anti-inflammatory, analgesic, and hepatoprotective properties. To better understand the biological mechanisms of iridoid compounds in this species, we performed a comprehensive analysis of the transcriptome and metabolome of P. rotata leaves from four different regions (3540-4270 m). Global metabolome profiling detected 575 metabolites, and 455 differentially accumulated metabolites (DAMs) were detected in P. rotata leaves from the four regions. Eight major DAMs related to iridoid metabolism in P. rotata leaves were investigated: shanzhiside methyl ester, 8-epideoxyloganic acid, barlerin, shanzhiside, geniposide, agnuside, feretoside, and catalpin. In addition, five soil physical and chemical indicators in P. rotata rhizosphere soils were analyzed. Four significant positive correlations were observed between alkaline nitrogen and geniposide, exchangeable calcium and geniposide, available potassium and shanzhiside, and available phosphorus and shanzhiside methyl ester. The transcriptome data showed 12 P. rotata cDNA libraries with 74.46 Gb of clean data, which formed 29,833 unigenes. Moreover, 78.91% of the unigenes were annotated using the eight public databases. Forty-one candidate genes representing 23 enzymes involved in the biosynthesis of iridoid compounds were identified in P. rotata leaves. Moreover, the DXS1, IDI1, 8-HGO1, and G10H2 genes associated with iridoid biosynthesis were specifically expressed in P. rotata. The integration of transcriptome and metabolome analyses highlights the crucial role of soil physical and chemical indicators and major gene expression related to iridoid metabolism pathways in P. rotata from different areas. Our findings provide a theoretical foundation for exploring the molecular mechanisms underlying iridoid compound accumulation in P. rotata.PMID:38931059 | DOI:10.3390/plants13121627

Plants (Basel). 2024 Jun 8;13(12):1600. doi: 10.3390/plants13121600.ABSTRACTRosa rugosa is highly regarded for its aesthetic and therapeutic qualities. In particular, R. rugosa's flowers are known to produce essential oils containing a mixture of volatile terpenes, phenylpropanoids, and other compounds. Despite this, extensive research exists on volatile terpenes in flowers, while the knowledge of non-volatile terpenes in distinct tissues is still limited. Using UPLC-ESI-MS/MS, a comprehensive analysis of the terpene metabolites in five different tissues of R. rugosa was conducted. These metabolites accumulated in distinct tissues, and the majority of them were triterpenoids. Transcriptome data were collected from five tissues using RNA-seq. Transcriptomics and metabolomics were utilized to evaluate the triterpene biosynthesis pathway, resulting in new insights into its regulation and biosynthesis. The RrOSC10 was identified as a key enzyme in converting 2,3-oxidosqualene into α-amyrin, potentially contributing to the triterpene biosynthesis pathway. Furthermore, the expression of the RrOSC10 gene was upregulated by salinity for 0.5 h and 1 h, with subsequent downregulation at 2 h. This study lays a foundation for future research on the biosynthesis and accumulation of triterpenes in R. rugosa.PMID:38931033 | DOI:10.3390/plants13121600

Plants (Basel). 2024 Jun 7;13(12):1594. doi: 10.3390/plants13121594.ABSTRACTPleurotus citrinopileatus Singer (PCS) has attracted increasing attention as a raw material for medicine and food. Its quality is greatly affected by the accumulation of metabolites, which varies with the applied drying methods. In this study, we utilize an approach based on ultra-high-performance liquid chromatography/Q Exactive mass spectrometry (UHPLC-QE-MS) to reveal the metabolic profiles of PCS from three different drying methods (natural air-drying, NAD; hot-air-drying, HAD; vacuum freeze-drying, VFD). The results showed that lipids, amino acids and their derivatives were all important secondary metabolites produced during NAD, HAD and VFD treatments, with the key differential metabolites of PCS during drying including fifteen lipids and seven amino acids. Meanwhile, VFD was the best way for long-term preservation of dried PCS. Hot-drying methods, especially HAD, can improve the medicinal component of PCS. Furthermore, KEGG enrichment analysis highlighted 16 pathways and indicated that amino acid metabolism might be the key metabolite pathway for the PCS drying process. Our study elucidates the relationship between drying methods and metabolites or metabolic pathways of PCS to determine the mechanisms affecting the quality of PCS, and finally provides reference values for further development and application in functional food and medications.PMID:38931026 | DOI:10.3390/plants13121594

Molecules. 2024 Jun 11;29(12):2781. doi: 10.3390/molecules29122781.ABSTRACTAn untargeted metabolomic study identified four potential lung cancer diagnostic biomarkers in human urine. One of the potential biomarkers was an unidentified feature possessing a m/z value of 561+. "561+" was isolated from human urine and tentatively identified as 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol glucuronide with unknown C24,25 stereochemistry using 1H NMR and mass spectrometry. In a prior report, the C24,25 stereochemistry of the aglycone, 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol, was found to be 24S,25R through GC analysis of the acetonide-TMS derivative. An authentic sample was prepared and found not to have the same stereochemistry as "561+". To identify the C24,25 stereochemistry, four C24,C25 diastereoisomeric alcohols of 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol were prepared from chiral amino acids. Using an LCMS method, the C24,C25 stereochemistry of the "561+" aglycone was determined to be 24R,25S. With the correct aglycone in hand, it was coupled with glucuronic acid to complete the first reported synthesis of 27-nor-5β-cholestane-3α,7α,12α,24R,25S pentol glucuronide. Deuterium labeled 27-nor-5β-cholestane-3α,7α,12α,24R,25S pentol was also synthesized for use as an internal standard for MS quantitation.PMID:38930845 | DOI:10.3390/molecules29122781

Molecules. 2024 Jun 11;29(12):2771. doi: 10.3390/molecules29122771.ABSTRACTThe development of the textile industry has negative effects on the natural environment. Cotton cultivation, dyeing fabrics, washing, and finishing require a lot of water and energy and use many chemicals. One of the most dangerous pollutants generated by the textile industry is dyes. Most of them are characterized by a complex chemical structure and an unfavorable impact on the environment. Especially azo dyes, whose decomposition by bacteria may lead to the formation of carcinogenic aromatic amines and raise a lot of concern. Using the metabolic potential of microorganisms that biodegrade dyes seems to be a promising solution for their elimination from contaminated environments. The development of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has allowed for a comprehensive approach to the processes occurring in cells. Especially multi-omics, which combines data from different biomolecular levels, providing an integrative understanding of the whole biodegradation process. Thanks to this, it is possible to elucidate the molecular basis of the mechanisms of dye biodegradation and to develop effective methods of bioremediation of dye-contaminated environments.PMID:38930836 | DOI:10.3390/molecules29122771

Molecules. 2024 Jun 9;29(12):2745. doi: 10.3390/molecules29122745.ABSTRACTDue to the intricate complexity of the original microbiota, residual heat-resistant enzymes, and chemical components, identifying the essential factors that affect dairy quality using traditional methods is challenging. In this study, raw milk, pasteurized milk, and ultra-heat-treated (UHT) milk samples were collectively analyzed using metagenomic next-generation sequencing (mNGS), high-throughput liquid chromatography-mass spectrometry (LC-MS), and gas chromatography-mass spectrometry (GC-MS). The results revealed that raw milk and its corresponding heated dairy products exhibited different trends in terms of microbiota shifts and metabolite changes during storage. Via the analysis of differences in microbiota and correlation analysis of the microorganisms present in differential metabolites in refrigerated pasteurized milk, the top three differential microorganisms with increased abundance, Microbacterium (p < 0.01), unclassified Actinomycetia class (p < 0.05), and Micrococcus (p < 0.01), were detected; these were highly correlated with certain metabolites in pasteurized milk (r > 0.8). This indicated that these genera were the main proliferating microorganisms and were the primary genera involved in the metabolism of pasteurized milk during refrigeration-based storage. Microorganisms with decreased abundance were classified into two categories based on correlation analysis with certain metabolites. It was speculated that the heat-resistant enzyme system of a group of microorganisms with high correlation (r > 0.8), such as Pseudomonas and Acinetobacter, was the main factor causing milk spoilage and that the group with lower correlation (r < 0.3) had a lower impact on the storage process of pasteurized dairy products. By comparing the metabolic pathway results based on metagenomic and metabolite annotation, it was proposed that protein degradation may be associated with microbial growth, whereas lipid degradation may be linked to raw milk's initial heat-resistant enzymes. By leveraging the synergy of metagenomics and metabolomics, the interacting factors determining the quality evolution of dairy products were systematically investigated, providing a novel perspective for controlling dairy processing and storage effectively.PMID:38930811 | DOI:10.3390/molecules29122745

Microorganisms. 2024 Jun 20;12(6):1241. doi: 10.3390/microorganisms12061241.ABSTRACTSigma factors are transcriptional regulators that are part of complex regulatory networks for major cellular processes, as well as for growth phase-dependent regulation and stress response. Actinoplanes sp. SE50/110 is the natural producer of acarbose, an α-glucosidase inhibitor that is used in diabetes type 2 treatment. Acarbose biosynthesis is dependent on growth, making sigma factor engineering a promising tool for metabolic engineering. ACSP50_0507 is a homolog of the developmental and osmotic-stress-regulating Streptomyces coelicolor σHSc. Therefore, the protein encoded by ACSP50_0507 was named σHAs. Here, an Actinoplanes sp. SE50/110 expression strain for the alternative sigma factor gene ACSP50_0507 (sigHAs) achieved a two-fold increased acarbose yield with acarbose production extending into the stationary growth phase. Transcriptome sequencing revealed upregulation of acarbose biosynthesis genes during growth and at the late stationary growth phase. Genes that are transcriptionally activated by σHAs frequently code for secreted or membrane-associated proteins. This is also mirrored by the severely affected cell morphology, with hyperbranching, deformed and compartmentalized hyphae. The dehydrated cell morphology and upregulation of further genes point to a putative involvement in osmotic stress response, similar to its S. coelicolor homolog. The DNA-binding motif of σHAs was determined based on transcriptome sequencing data and shows high motif similarity to that of its homolog. The motif was confirmed by in vitro binding of recombinantly expressed σHAs to the upstream sequence of a strongly upregulated gene. Autoregulation of σHAs was observed, and binding to its own gene promoter region was also confirmed.PMID:38930623 | DOI:10.3390/microorganisms12061241

Microorganisms. 2024 May 27;12(6):1077. doi: 10.3390/microorganisms12061077.ABSTRACTIn this study, we investigated the correlation between the composition and function of the gut microbiota and the semen quality of Rongchang boars. Significant differences in gut microbial composition between boars with high (group H) and low (group L) semen utilization rates were identified through 16S rRNA gene sequencing, with 18 differential microbes observed at the genus level. Boars with lower semen utilization rates exhibited a higher relative abundance of Treponema, suggesting its potential role in reducing semen quality. Conversely, boars with higher semen utilization rates showed increased relative abundances of Terrisporobacter, Turicibacter, Stenotrophomonas, Clostridium sensu stricto 3, and Bifidobacterium, with Stenotrophomonas and Clostridium sensu stricto 3 showing a significant positive correlation with semen utilization rates. The metabolomic analyses revealed higher levels of gluconolactone, D-ribose, and 4-pyridoxic acid in the H group, with 4 pyridoxic acid and D-ribose showing a significant positive correlation with Terrisporobacter and Clostridium sensu stricto 3, respectively. In contrast, the L group showed elevated levels of D-erythrose-4-phosphate, which correlated negatively with Bifidobacterium and Clostridium sensu stricto 3. These differential metabolites were enriched in the pentose phosphate pathway, vitamin B6 metabolism, and antifolate resistance, potentially influencing semen quality. These findings provide new insights into the complex interplay between the gut microbiota and boar reproductive health and may offer important information for the discovery of disease biomarkers and reproductive health management.PMID:38930459 | DOI:10.3390/microorganisms12061077

Microorganisms. 2024 May 21;12(6):1033. doi: 10.3390/microorganisms12061033.ABSTRACTCompared to commercial breeds, Chinese local pig breeds have a greater ability to digest dietary fiber, which may be due to differences in intestinal microbiota. In this study, we fed Ding'an and DLY pigs high and low levels of dietary fiber, respectively, to investigate factors contributing to high dietary fiber adaption in Ding'an pigs. Twelve Ding'an pigs and DLY pigs were randomly divided into a 2 (diet) × 2 (breed) factorial experiment (n = 3). Compared with commercial pigs, Ding'an pigs have a stronger ability to digest dietary fiber. Prevotella was more prevalent in Ding'an pigs than in DLY pigs, which may be an important reason for the stronger ability of fiber degradation in Ding'an pigs. When the effects of feed and breed factors are considered, differences in abundance of 31 species and 14 species, respectively, may result in a greater ability of fiber degradation in Ding'an pigs. Among them, Prevotella. sp. CAG:520 may be a newly discovered bacterium related to fiber degradation, which positively correlated with many fiber-degrading bacteria (r > 0.7). We also found that the concentration of plant metabolites with anti-inflammatory and antioxidant effects was higher in the colonic chyme of Ding'an pigs after increasing the fiber content, which resulted in the downregulated expression of inflammatory factors in colonic mucosa. Spearman's correlation coefficient revealed a strong correlation between microbiota and the apparent digestibility of dietary fiber (r > 0.7). The mRNA expressions of SLC16A1, PYY, and GCG were significantly increased in the colonic mucosa of Ding'an pigs fed on high-fiber diets, which indicates that Ding'an pigs have an enhanced absorption of SCFAs. Our results suggested that an appropriate increase in dietary fiber content can reduce the inflammatory response and improve feed efficiency in Ding'an pigs, and differences in the intestinal microbial composition may be an important reason for the difference in the fiber degradation capacity between the two breeds of pigs.PMID:38930415 | DOI:10.3390/microorganisms12061033

Life (Basel). 2024 May 29;14(6):698. doi: 10.3390/life14060698.ABSTRACTINTRODUCTION: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results.METHODS: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells.RESULTS: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis.CONCLUSIONS: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC.PMID:38929681 | DOI:10.3390/life14060698

Animals (Basel). 2024 Jun 19;14(12):1824. doi: 10.3390/ani14121824.ABSTRACTThe present study aimed to investigate the impacts of dietary standardized ileal digestible lysine to net energy (SID Lys:NE) ratio on lipid metabolism in pigs fed high-wheat diets. Thirty-six crossbred growing barrows (65.20 ± 0.38 kg) were blocked into two treatment groups, fed high-wheat diets with either a high SID Lys:NE ratio (HR) or a low SID Lys:NE ratio (LR). Each treatment group consisted of three replicates, with six pigs per pen in each replicate. The diminishing dietary SID Lys:NE ratio exhibited no adverse impacts on the carcass trait (p > 0.05) but increased the marbling score of the longissimus dorsi muscle (p < 0.05). Meanwhile, LR diets tended to increase the serum triglyceride concentration (p < 0.1). LR diets upregulated fatty acid transport protein 4 and acetyl-coA carboxylase α expression levels and downregulated the expression level of adipose triglyceride lipase (p < 0.05). LR diets improved energy metabolism via decreasing the expression levels of AMP-activated protein kinase (AMPK) α1, sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) (p < 0.05). Additionally, LR diets stimulated hepatic bile acid synthesis via upregulating the expression levels of cytochrome P450 family 7 subfamily A member 1 and cytochrome P450 family 27 subfamily A member 1, and downregulating farnesol X receptor (FXR) and small heterodimer partner (SHP) expression levels (p < 0.05). A lowered SID Lys:NE ratio affected the colonic microbial composition, characterized by increased relative abundances of YRC22, Parabacteroides, Sphaerochaeta, and Bacteroides, alongside a decreased in the proportion of Roseburia, f_Lachnospiraceae_g_Clostridium, Enterococcus, Shuttleworthia, Exiguobacterium, Corynebacterium, Subdoligranulum, Sulfurospirillum, and Marinobacter (p < 0.05). The alterations in microbial composition were accompanied by a decrease in colonic butyrate concentration (p < 0.1). The metabolomic analysis revealed that LR diets affected primary bile acid synthesis and AMPK signaling pathway (p < 0.05). And the mantel analysis indicated that Parabacteroides, Sphaerochaeta, f_Lachnospiraceae_g_Clostridium, Shuttleworthia, and Marinobacter contributed to the alterations in body metabolism. A reduced dietary SID Lys:NE ratio improves energy metabolism, stimulates lipogenesis, and inhibits lipolysis in finishing pigs by regulating the AMPKα/SIRT1/PGC-1α pathway and the FXR/SHP pathway. Parabacteroides and Sphaerochaeta benefited bile acids synthesis, whereas f_Lachnospiraceae_g_Clostridium, Shuttleworthia, and Marinobacter may contribute to the activation of the AMPK signaling pathway. Overall, body metabolism and colonic microbiota collectively controlled the lipid metabolism in finishing pigs.PMID:38929443 | DOI:10.3390/ani14121824

Antioxidants (Basel). 2024 Jun 20;13(6):744. doi: 10.3390/antiox13060744.ABSTRACTSelenosugars are gaining growing interest due to their antioxidant efficacy, and their ability to inhibit glycosidases, repair skin tissue or reduce endothelial dysfunction. Among selenosugars, those in which selenium replaces heterocyclic oxygen in a 5-membered sugar were our focus, and their coupling with phenolic compounds appears to be a strategy aimed at producing new compounds with enhanced antioxidant efficacy. In this context, the Mitsunobu reaction has been advantageously explored to obtain trans-p-coumaroyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, trans-caffeoyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, and trans-feruloyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose. These compounds underwent removal of the iso-propylidene group, to provide the corresponding hydroxycinnamoyl-1,4-deoxy-4-seleno-d-ribose. All compounds were characterized by Nuclear Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). This latter technique was pivotal for ensuing cellular metabolomics analyses. In fact, after evaluating the anti-radical efficacy through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, which underline the massive role of the phenolic moiety in establishing efficacy, the compounds, whose cytotoxicity was first screened in two highly oxidative-stress-sensitive cells, were tested for their wound healing properties towards human HaCaT keratinocytes cells. Caffeoyl- and feruloyl selenosugars exerted a dose-dependent repair activity, while, as highlighted by the metabolomic approach, they were poorly taken up within the cells.PMID:38929184 | DOI:10.3390/antiox13060744

Antioxidants (Basel). 2024 Jun 14;13(6):724. doi: 10.3390/antiox13060724.ABSTRACTOleuropein (OLE), a phenolic compound particularly abundant in the olive leaves, has been reported to have beneficial activities against colorectal cancer (CRC). In vitro studies suggested that these latter could be due to a modulation of the intestinal microbiota. Aiming to evaluate if OLE could affect the intestinal microbiota and the plasma metabolome, an antioxidant oleuropein-rich leaf extract (ORLE) was administered for one week to PIRC rats (F344/NTac-Apcam1137), a genetic model mimicking CRC. ORLE treatment significantly modulated the gut microbiota composition. Plasma metabolomic profiles revealed a significant predictive ability for amino acids, medium-chain fatty acids, and aldehydes. Pathway analysis revealed a significant decrease in phosphatidylcholine accumulation (LogFC = -1.67) in PIRC rats. These results suggest a significant effect of ORLE administration on faecal microbiota profiles and plasma metabolomes, thereby offering new omics-based insights into its protective role in CRC progression.PMID:38929163 | DOI:10.3390/antiox13060724

Antioxidants (Basel). 2024 Jun 11;13(6):708. doi: 10.3390/antiox13060708.ABSTRACTLycium barbarum, commonly recognized as goji berry or wolfberry, is highly appreciated not only for its organoleptic and nutritional properties but also as an important source of bioactive compounds such as polysaccharides, carotenoids, phenolics, and various other non-nutritive compounds. These constituents give it a multitude of health benefits, including antioxidant, anti-inflammatory, and anticancer properties. However, the precise biochemical mechanisms responsible for its anticancer effects remain unclear, and the comprehensive composition of goji berry extracts is often insufficiently explored. This study aimed to investigate the biochemical pathways modulated in breast cancer cells by an ethanolic extract of Lycium barbarum fruit (LBE). Following metabolomic profiling using UHPLC-HRMS/MS, we assessed the antitumoral properties of LBE on different breast cancer cell lines. This investigation revealed that LBE exhibited cytotoxic effects, inducing a pro-oxidant effect that triggered pyroptosis activation through endoplasmic reticulum (ER) stress and subsequent activation of the P-IRE1α/XBP1/NLRP3 axis in MCF-7 cells. In addition, LBE did not display cytotoxicity toward healthy human cells but demonstrated antioxidant properties by neutralizing ROS generated by doxorubicin. These findings underscore the potential of LBE as a highly promising natural extract in cancer therapy.PMID:38929147 | DOI:10.3390/antiox13060708

Toxicology. 2024 Jun 24:153871. doi: 10.1016/j.tox.2024.153871. Online ahead of print.ABSTRACTFmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.PMID:38925359 | DOI:10.1016/j.tox.2024.153871

J Ethnopharmacol. 2024 Jun 24:118487. doi: 10.1016/j.jep.2024.118487. Online ahead of print.ABSTRACTNonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear OBJECTIVE: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms METHODS: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα RESULTS: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA CONCLUSIONS: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.PMID:38925322 | DOI:10.1016/j.jep.2024.118487

Environ Toxicol Pharmacol. 2024 Jun 24:104494. doi: 10.1016/j.etap.2024.104494. Online ahead of print.ABSTRACTAssessing the harm caused by pollutants in urban ecosystems remains a significant challenge. Traditional ecotoxicological endpoints are often not sensitive enough to detect the effects of toxicants at environmentally relevant concentrations (≤ng/L). A potential solution is using molecular biology methods to look at small biochemical changes caused by exposure to ng/L concentrations of contaminants. This has been tested in the lab but not conclusively demonstrated in the field. We exposed the freshwater amphipod (Austrochiltonia subtenuis) to water from an urban wetland containing known concentrations of per-and polyfluoroalkyl substances (as well as very low concentrations of pesticides) for 14 days and analyzed their metabolite profiles. Mannose, Myo-inositol, and Isopropyl propionate were found to change in PFAS exposed amphipods, a similar response to that previously observed in laboratory exposures to the same PFAS, but not pesticides. The results give a better understanding of PFAS toxicity at environmentally relevant concentrations and conditions.PMID:38925282 | DOI:10.1016/j.etap.2024.104494

Chem Biol Interact. 2024 Jun 24:111118. doi: 10.1016/j.cbi.2024.111118. Online ahead of print.ABSTRACTNicotinamide riboside (NR) is a precursor and exogenous supplement of nicotinamide adenine dinucleotide (NAD+). NR has been shown to play a beneficial role in a variety of neurodegenerative diseases. A phase 1 clinical trial identified NR as a potential neuroprotective therapy for Parkinson's disease (PD). However, the mechanism of action of NR in PD has not been fully elucidated. Therefore, the present study aimed to investigate the potential effects of NR on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish and its underlying mechanisms. The results showed that NR improved motor dysfunction, survival time, dopamine neurons, and peripheral neurons, as well as the NAD+ levels in the MPTP-affected PD zebrafish model. In addition, transcriptome sequencing analysis revealed that, after NR treatment, differentially expressed genes were significantly enriched in the glucose metabolism and protein processing pathways in the endoplasmic reticulum (ER). Quantitative PCR (qPCR) revealed that the mRNA levels of the glycoheterotrophic enzyme (involved in glucose metabolism) were significantly decreased, and the glycolytic enzyme mRNA expression levels were significantly increased. The results of the non-targeted metabolomic analysis showed that NR treatment significantly increased the levels of metabolites such as nicotinic acid and nicotinamide, in addition to α-D-glucose from the gluconeogenesis and glycolysis metabolism pathways and some of the glucogenic amino acids, such as glutamine. Importantly, NR ameliorated MPTP-induced endoplasmic reticulum stress (ERS) in the PD zebrafish model through the Perk-Eif2α-Atf4-Chop pathway. These results highlight the neuroprotective effect of NR in the present PD zebrafish model through modulation of glucose metabolism and ER stress via the Perk-Eif2α-Atf4-Chop pathway and provide valuable mechanistic insights into the treatment of PD.PMID:38925209 | DOI:10.1016/j.cbi.2024.111118

Int J Biol Macromol. 2024 Jun 24:133348. doi: 10.1016/j.ijbiomac.2024.133348. Online ahead of print.ABSTRACTSoluble dietary fibre (SDF) has gained growing interest because of its multiple functional and nutritional benefits. In the current study, the effect of SDF extracted from eucheuma seaweed on both the physicochemical properties and the released metabolites of yellow cakes was evaluated systematically. The results revealed that the addition of SDF induced increases in specific gravity, specific volume and water content of yellow cakes, and caused a decrease in weight loss and changes in texture and colour. In addition, sensory evaluation showed that up to 10 % substitution of flour with SDF was acceptable. In vitro digestion of cakes demonstrated that flour substitution with SDF at different levels (8 %-14 %) significantly reduced the release of glucose, ranging from 11.24 % to 29.12 %. In addition to the increased apparent viscosity of the cake digesta, the metabolite analysis based on nuclear magnetic resonance spectroscopy identified a total of 29 metabolites, including amino acids, fatty acids and sugars. Notably, the addition of SDF reduced the release of amino acids and fatty acids after digestion. These findings suggested that seaweed SDF was a potential substitute for some food components, which would provide functional benefits to the digestive characteristics.PMID:38925174 | DOI:10.1016/j.ijbiomac.2024.133348