Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Study on the correlation between color and taste of beauty tea infusion and the pivotal contributing compounds based on UV-visible spectroscopy, taste equivalent quantification and metabolite analysis

Fri, 23/02/2024 - 12:00
Food Chem X. 2024 Feb 5;21:101192. doi: 10.1016/j.fochx.2024.101192. eCollection 2024 Mar 30.ABSTRACTThis study utilized a colorimeter to determine the color values of 23 beauty tea (BT) samples, the color and the taste characteristics were also quantitatively described through ultraviolet-visible (UV-Vis) spectroscopy and taste equivalent quantification. Furthermore, metabolomic analysis was conducted by using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS). Correlation analysis was employed to preliminarily identify the compounds that contribute to the color and taste of BT infusion. Finally, the contributing compounds were further determined through verification experiment. The results showed that within a certain range, as the color of BT infusion deepened, the taste became stronger, more bitter and astringent, while on the contrary, it became sweeter and mellower. Theaflavins, kaempferol, astragalin, and 5-p-coumaroylquinic acid influenced both the color and taste of the BT infusion. Gallic acid was also determined as a contributor to the color. This study provides new insights into research on tea quality in infusion color and taste aspects.PMID:38389575 | PMC:PMC10881530 | DOI:10.1016/j.fochx.2024.101192

Integrated metabolome and microbiome analysis reveals the effect of rumen-protected sulfur-containing amino acids on the meat quality of Tibetan sheep meat

Fri, 23/02/2024 - 12:00
Front Microbiol. 2024 Feb 8;15:1345388. doi: 10.3389/fmicb.2024.1345388. eCollection 2024.ABSTRACTINTRODUCTION: This study investigated the effects of rumen-protected sulfur-containing amino acids (RPSAA) on the rumen and jejunal microbiota as well as on the metabolites and meat quality of the longissimus lumborum (LL) in Tibetan sheep.METHODS: By combining 16S rDNA sequencing with UHPLC-Q-TOF MS and Pearson correlation analysis, the relationship between gastrointestinal microbiota, muscle metabolites and meat quality was identified.RESULTS: The results showed that feeding RPSAA can increase the carcass weight, abdominal fat thickness (AP-2 group), and back fat thickness (AP-2 and AP-3 group) of Tibetan sheep. The water holding capacity (WHC), texture, and shear force (SF) of LL in the two groups also increased although the fatty acids content and brightness (L*) value significantly decreased in the AP-2 group. Metabolomics and correlation analysis further showed that RPSAA could significantly influence the metabolites in purine metabolism, thereby affecting L* and SF. In addition, RPSAA was beneficial for the fermentation of the rumen and jejunum. In both groups, the abundance of Prevotella 1, Lachnospiraceae NK3A20 group, Prevotella UCG-003, Lachnospiraceae ND3007 group in the rumen as well as the abundance of Eubacterium nodatum group and Mogibacterium group in the jejunum increased. In contrast, that of Turicibacter pathogens in the jejunum was reduced. The above microorganisms could regulate meat quality by regulating the metabolites (inosine, hypoxanthine, linoleic acid, palmitic acid, etc.) in purine and fatty acids metabolism.DISCUSSION: Overall, reducing the levels of crude proteins in the diet and feeding RPSAA is likely to improve the carcass quality of Tibetan sheep, with the addition of RPMET (AP-2) yielding the best edible quality, possibly due to its ability to influence the gastrointestinal microbiota to subsequently regulate muscle metabolites.PMID:38389537 | PMC:PMC10883651 | DOI:10.3389/fmicb.2024.1345388

Alternative electrolyte solutions for untargeted breath metabolomics using secondary-electrospray ionization high-resolution mass spectrometry

Fri, 23/02/2024 - 12:00
Rapid Commun Mass Spectrom. 2024 Apr 30;38(8):e9714. doi: 10.1002/rcm.9714.ABSTRACTRATIONALE: Secondary-electrospray ionization (SESI) coupled with high-resolution mass spectrometry is a powerful tool for the discovery of biomarkers in exhaled breath. A primary electrospray consisting of aqueous formic acid (FA) is currently used to charge the volatile organic compounds in breath. To investigate whether alternate electrospray compositions could enable different metabolite coverage and sensitivities, the electrospray dopants NaI and AgNO3 were tested.METHODS: In a proof-of-principle manner, the exhaled breath of one subject was analyzed repeatedly with different electrospray solutions and with the help of a spectral stitching technique. Capillary diameter and position were optimized to achieve proper detection of exhaled breath. The detected features were then compared using formula annotation. Using an evaporation-based gas standard system, the signal response of the different solutions was probed.RESULTS: Principal component analysis revealed a substantial difference in features detected with AgNO3 . With silver, more sulfur-containing features and more unsaturated hydrocarbon compounds were detected. Furthermore, more primary amines were potentially ionized, as indicated by van Krewelen diagrams. In total, twice as many features were unique to AgNO3 than for other electrospray dopants. Using gas standards at known concentrations, the high sensitivity of FA as a dopant was demonstrated but also indicated alternate sensitivities of the other electrospray solutions.CONCLUSIONS: This work demonstrated the potential of AgNO3 as a complementary dopant for further biomarker discovery in SESI-based breath analysis.PMID:38389333 | DOI:10.1002/rcm.9714

Dietary chlorogenic acid alleviates high-fat diet-induced steatotic liver disease by regulating metabolites and gut microbiota

Fri, 23/02/2024 - 12:00
Int J Food Sci Nutr. 2024 Feb 22:1-16. doi: 10.1080/09637486.2024.2318590. Online ahead of print.ABSTRACTThe high-fat diet would lead to excessive fat storage in the liver to form metabolic dysfunction-associated steatotic liver disease (MASLD), and the trend is burgeoning. The aim of the study is to investigate the effects of chlorogenic acid (CGA) on metabolites and gut microorganisms in MASLD mice induced by a high-fat diet. In comparison to the HF group, the TC (total cholesterol), TG (total triglycerides), LDL-C (low-density lipoprotein cholesterol), AST (aspartate aminotransferase) and ALT (alanine transaminase) levels were reduced after CGA supplement. CGA led to an increase in l-phenylalanine, l-tryptophan levels, and promoted fatty acid degradation. CGA increased the abundance of the Muribaculaceae, Bacteroides and Parabacteroides. Changes in these microbes were significantly associated with the liver metabolites level and lipid profile level. These data suggest important roles for CGA regulating the gut microbiota, liver and caecum content metabolites, and TG-, TC- and LDL-C lowering function.PMID:38389248 | DOI:10.1080/09637486.2024.2318590

Author Correction: A heterotypic assembly mechanism regulates CHIP E3 ligase activity

Thu, 22/02/2024 - 12:00
EMBO J. 2024 Feb 22. doi: 10.1038/s44318-024-00042-3. Online ahead of print.NO ABSTRACTPMID:38388749 | DOI:10.1038/s44318-024-00042-3

Ultrasound-activated piezo-hot carriers trigger tandem catalysis coordinating cuproptosis-like bacterial death against implant infections

Thu, 22/02/2024 - 12:00
Nat Commun. 2024 Feb 22;15(1):1643. doi: 10.1038/s41467-024-45619-y.ABSTRACTImplant-associated infections due to the formation of bacterial biofilms pose a serious threat in medical healthcare, which needs effective therapeutic methods. Here, we propose a multifunctional nanoreactor by spatiotemporal ultrasound-driven tandem catalysis to amplify the efficacy of sonodynamic and chemodynamic therapy. By combining piezoelectric barium titanate with polydopamine and copper, the ultrasound-activated piezo-hot carriers transfer easily to copper by polydopamine. It boosts reactive oxygen species production by piezoelectrics, and facilitates the interconversion between Cu2+ and Cu+ to promote hydroxyl radical generation via Cu+ -catalyzed chemodynamic reactions. Finally, the elevated reactive oxygen species cause bacterial membrane structure loosening and DNA damage. Transcriptomics and metabolomics analysis reveal that intracellular copper overload restricts the tricarboxylic acid cycle, promoting bacterial cuproptosis-like death. Therefore, the polyetherketoneketone scaffold engineered with the designed nanoreactor shows excellent antibacterial performance with ultrasound stimulation and promotes angiogenesis and osteogenesis on-demand in vivo.PMID:38388555 | DOI:10.1038/s41467-024-45619-y

Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis

Thu, 22/02/2024 - 12:00
Nat Commun. 2024 Feb 22;15(1):1617. doi: 10.1038/s41467-024-45473-y.ABSTRACTPeriodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis.PMID:38388542 | DOI:10.1038/s41467-024-45473-y

Differential effects of elevated CO2 on awn and glume metabolism in durum wheat (Triticum durum)

Thu, 22/02/2024 - 12:00
Funct Plant Biol. 2024 Feb 23. doi: 10.1071/FP23255. Online ahead of print.ABSTRACTWhile the effect of CO2 enrichment on wheat (Triticum spp.) photosynthesis, nitrogen content or yield has been well-studied, the impact of elevated CO2 on metabolic pathways in organs other than leaves is poorly documented. In particular, glumes and awns, which may refix CO2 respired by developing grains and be naturally exposed to higher-than-ambient CO2 mole fraction, could show specific responses to elevated CO2. Here, we took advantage of a free-air CO2 enrichment experiment and performed multilevel analyses, including metabolomics, ionomics, proteomics, major hormones and isotopes in Triticum durum. While in leaves, elevated CO2 tended to accelerate amino acid metabolism with many significantly affected metabolites, the effect on glumes and awns metabolites was modest. There was a lower content in compounds of the polyamine pathway (along with uracile and allantoin) under elevated CO2, suggesting a change in secondary N metabolism. Also, cytokinin metabolism appeared to be significantly affected under elevated CO2. Despite this, elevated CO2 did not affect the final composition of awn and glume organic matter, with the same content in carbon, nitrogen and other elements. We conclude that elevated CO2 mostly impacts on leaf metabolism but has little effect in awns and glumes, including their composition at maturity.PMID:38388529 | DOI:10.1071/FP23255

Mechanism of intestinal microbiota disturbance promoting the occurrence and development of esophageal squamous cell carcinoma--based on microbiomics and metabolomics

Thu, 22/02/2024 - 12:00
BMC Cancer. 2024 Feb 22;24(1):245. doi: 10.1186/s12885-024-11982-8.ABSTRACTEsophageal squamous cell carcinoma (ESCC) is a high-risk malignant tumor that has been reported in China. Some studies indicate that gut microbiota disorders can affect the occurrence and development of ESCC, but the underlying mechanism remains unclear. In this study, we aimed to explore the possible underlying mechanisms using microbiomics and metabolomics. Fifty ESCC patients and fifty healthy controls were selected as the study subjects according to sex and age, and fecal samples were collected. 16S rDNA sequencing and LC‒MS were used for microbiomics and nontargeted metabolomics analyses. We found significant differences in the composition of the gut microbiota and metabolites between the ESCC patients and control individuals (P < 0.05). ESCC patients exhibited increased abundances of Fusobacteriaceae and Lactobacillus, increased levels of GibberellinA34 and decreased levels of 12-hydroxydodecanoic acid; these metabolites could be diagnostic and predictive markers of ESCC. An increase in the abundance of Enterobacteriaceae and Lactobacillus significantly reduced the content of L-aspartate and pantothenic acid, which may be involved in the occurrence and development of ESCC by downregulating the expression of proteins in the pantothenate and coenzyme A biosynthesis pathways. An imbalance in the intestinal flora may decrease the number of eosinophils in peripheral blood, resulting in the activation of an inflammatory response and immune dysfunction, leading to ESCC deterioration. We hypothesize that this imbalance in the gut microbiota can cause an imbalance in intestinal metabolites, which can activate carcinogenic metabolic pathways, affect inflammation and immune function, and play a role in the occurrence and development of ESCC.PMID:38388357 | DOI:10.1186/s12885-024-11982-8

Refining GFR estimation: a quest for the unobservable truth?

Thu, 22/02/2024 - 12:00
Kidney Int. 2024 Mar;105(3):435-437. doi: 10.1016/j.kint.2023.12.004.ABSTRACTAssessing glomerular filtration rate (GFR), which is central to evaluating kidney health, remains challenging. Measured GFR is not widely available and lacks standardization. Estimated GFR can be highly inaccurate for some patients and has limited applicability to many patient populations, such as those who are acutely ill. Recent metabolomic advances show promise for identifying new filtration markers that might enhance GFR estimation. Improving GFR assessment will require refinement in both GFR measurement and estimation methods.PMID:38388142 | DOI:10.1016/j.kint.2023.12.004

Biological age as estimated by baseline circulating metabolites is associated with incident diabetes and mortality

Thu, 22/02/2024 - 12:00
J Nutr Health Aging. 2024 Feb;28(2):100032. doi: 10.1016/j.jnha.2023.100032. Epub 2024 Jan 2.ABSTRACTOBJECTIVES: It is unclear how metabolomic assessment of biological aging performs in non-White populations and whether such an approach can predict future mortality. We aimed to evaluate the application of serum metabolomics combined with machine learning methodologies to predict incident diabetes and mortality in a Thai population.DESIGN, SETTING AND PARTICIPANTS: We analyzed serum samples and mortality data over 11 years from among 454 participants with no previous history of diabetes and with a fasting plasma glucose ≥85th percentile (5.4 mmol/L) but <7 mmol/L.MEASUREMENTS: Untargeted serum metabolomics were assessed using liquid chromatography/mass spectrometry. A deep artificial neural network was used to predict biological age based on serum metabolite profiles and chronological age.RESULTS: The mean age of participants was 40.5 ± 6.4 years, and 70.8% were men. We found a significant positive correlation between metabolomic age and chronological age (r = 0.71, P < 0.001). After 5 years, 61 of 404 participants with available glycated hemoglobin status (15.1%) progressed to diabetes. Chronological age was associated with incident diabetes but was not significant (P = 0.08), after adjusting for BMI and sex. Metabolomic age was significantly related to incident diabetes after controlling for BMI and sex (P < 0.05). Over the 11-year follow-up, 10 participants died owing to non-accidental causes. When metabolomic age and chronological age were included together in the model, metabolomic age (but not chronological age) was associated with mortality, independent of age, sex, and BMI. Among all identifiable metabolites, beta-D-mannosylphosphodecaprenyl and phosphatidylserines were the five leading metabolites associated with mortality.CONCLUSION: We concluded that serum metabolomic profile was associated with incident diabetes as well as mortality over our 11-year study period, which may render it potentially useful in assessing biological aging in humans.PMID:38388109 | DOI:10.1016/j.jnha.2023.100032

Neutrophil elastase-dependent cleavage of LTA4H alters its aminopeptidase activity in cystic fibrosis

Thu, 22/02/2024 - 12:00
Eur Respir J. 2024 Feb 22:2301512. doi: 10.1183/13993003.01512-2023. Online ahead of print.NO ABSTRACTPMID:38387968 | DOI:10.1183/13993003.01512-2023

Microbial lipid synthesis based on visible light-driven oxygen doped-graphitic carbon nitride /oleaginous yeast hybrid system

Thu, 22/02/2024 - 12:00
Bioresour Technol. 2024 Feb 20:130476. doi: 10.1016/j.biortech.2024.130476. Online ahead of print.ABSTRACTThe use of solar energy and heterotrophic microbes to synthesize microbial lipids is a promising strategy to solve energy crisis and reduce CO2 emissions. In this study, a photocatalyst, oxygen-doped graphitic carbon nitride (O-g-C3N4), was synthesized and combined with an oleaginous yeast strain, Cutaneotrichosporon dermatis ZZ-46, to construct a photocatalyst-microbe hybrid (PMH) system. Under illumination, the lipid yield of the PMH system reached 1.61 g/L after 96 h (87 % higher than that of control). NADPH/NADP+ ratio of ZZ-46 cells in the PMH system increased. Metabolomics results revealed that glutathione generation was increased, and the fatty acid decomposition pathway in ZZ-46 cells was inhibited in the PMH system. This study provides a new approach for the synthesis of microbial lipids based on solar energy and heterotrophic microbes.PMID:38387842 | DOI:10.1016/j.biortech.2024.130476

Maternal exposure to polystyrene nanoplastics causes defective retinal development and function in progeny mice by disturbing metabolic profiles

Thu, 22/02/2024 - 12:00
Chemosphere. 2024 Feb 20:141513. doi: 10.1016/j.chemosphere.2024.141513. Online ahead of print.ABSTRACTMicroplastics (MPs) and nanoplastics (NPs) are widely spreading in our living environment, accumulating in the human body and potentially threating human health. The retina, which is a terminally differentiated extension of the central nervous system, is essential for the visual system. However, the effects and molecular mechanisms of MPs/NPs on retina development and function are still unclear. Here, we investigated the effects and modes of action of polystyrene NPs (PS-NPs) on the retina using mice as a mammalian model species. Maternal PS-NP exposure (100 nm) at an environmentally realistic concentration of 10 mg L-1 (or 2.07 *1010 particles mL-1) via drinking water from the first day of pregnancy till the end of lactation (21 days after birth) caused defective neural retinal development in the neonatal mice, by depositing in the retinal tissue and reducing the number of retinal ganglion cells and bipolar cells. Exposure to PS-NPs retarded retinal vascular development, while abnormal electroretinogram (ERG) responses and an increased level of oxidative stress were also observed in the retina of the progeny mice after maternal PS-NP exposure. Metabolomics showed significant dysregulation of amino acids that are pivotal to neuron retinal function, such as glutamate, aspartate, alanine, glycine, serine, threonine, taurine, and serotonin. Transcriptomics identified significantly dysregulated genes, which were enriched in processes of angiogenesis, visual system development and lens development. Regulatory analysis showed that Fos gene mediated pathways could be a potential key target for PS-NP exposure in retinal development and function. Our study revealed that maternal exposure to PS-NPs generated detrimental effects on retinal development and function in progeny mice, offering new insights into the visual toxicity of PS-NPs.PMID:38387657 | DOI:10.1016/j.chemosphere.2024.141513

Microbiological and metabolic pathways analysing the mechanisms of alfalfa polysaccharide and sulfated alfalfa polysaccharide in alleviating obesity

Thu, 22/02/2024 - 12:00
Int J Biol Macromol. 2024 Feb 20:130334. doi: 10.1016/j.ijbiomac.2024.130334. Online ahead of print.ABSTRACTAlfalfa polysaccharide (AP) and sulfated alfalfa polysaccharide (SAP) exhibit potential for alleviating obesity. This study aimed to analyze the mechanism of action of AP and SAP in alleviating obesity through combined microbiomics and metabolomics. The research selected validated optimal AP and SAP concentration for experiment. The results showed that AP and SAP down-regulated colonic inflammatory gene expression, regulated intestinal pH to normal, and restored intestinal growth. Microbial sequencing showed that AP and SAP altered the microbial composition ratio. AP increased the relative abundance of Muribaculaceae and Romboutsia. SAP increased the relative abundance of Dubosiella, Fecalibaculum and Desulfovibrionaceae. Metabolomic analysis showed that AP regulated steroid hormone biosynthesis, neuroactive ligand-receptor interactions and bile secretion pathways. SAP focuses more on pathways related to amino acid metabolism. Meanwhile, AP and SAP down-regulated the mRNA expression of colonic COX-2, PepT-1 and HK2 and up-regulated the mRNA expression of TPH1. Correlation analysis showed a strong correlation between metabolites and gut bacteria. Dubosiella, Faecalibaculum may be the critical marker flora for polysaccharides to alleviate obesity. This study indicates that AP and SAP alleviate obesity through different pathways and that specific polysaccharide modifications affect characteristic microbial and metabolic pathways, providing new insights into polysaccharide modifications.PMID:38387635 | DOI:10.1016/j.ijbiomac.2024.130334

Strategies for mitigation of pesticides from the environment through alternative approaches: A review of recent developments and future prospects

Thu, 22/02/2024 - 12:00
J Environ Manage. 2024 Feb 21;354:120326. doi: 10.1016/j.jenvman.2024.120326. Online ahead of print.ABSTRACTChemical-based peticides are having negative impacts on both the healths of human beings and plants as well. The World Health Organisation (WHO), reported that each year, >25 million individuals in poor nations are having acute pesticide poisoning cases along with 20,000 fatal injuries at global level. Normally, only ∼0.1% of the pesticide reaches to the intended targets, and rest amount is expected to come into the food chain/environment for a longer period of time. Therefore, it is crucial to reduce the amounts of pesticides present in the soil. Physical or chemical treatments are either expensive or incapable to do so. Hence, pesticide detoxification can be achieved through bioremediation/biotechnologies, including nano-based methodologies, integrated approaches etc. These are relatively affordable, efficient and environmentally sound methods. Therefore, alternate strategies like as advanced biotechnological tools like as CRISPR Cas system, RNAi and genetic engineering for development of insects and pest resistant plants which are directly involved in the development of disease- and pest-resistant plants and indirectly reduce the use of pesticides. Omics tools and multi omics approaches like metagenomics, genomics, transcriptomics, proteomics, and metabolomics for the efficient functional gene mining and their validation for bioremediation of pesticides also discussed from the literatures. Overall, the review focuses on the most recent advancements in bioremediation methods to lessen the effects of pesticides along with the role of microorganisms in pesticides elimination. Further, pesticide detection is also a big challenge which can be done by using HPLC, GC, SERS, and LSPR ELISA etc. which have also been described in this review.PMID:38387349 | DOI:10.1016/j.jenvman.2024.120326

Dietary tryptophan alleviates intestinal inflammation caused by long photoperiod via gut microbiota derived tryptophan metabolites-NLRP3 pathway in broiler chickens

Thu, 22/02/2024 - 12:00
Poult Sci. 2024 Jan 29;103(4):103509. doi: 10.1016/j.psj.2024.103509. Online ahead of print.ABSTRACTLight pollution is a potential risk factor for intestinal health. Tryptophan plays an important role in the inhibition of intestinal inflammation. However, the mechanism of tryptophan in alleviating intestinal inflammation caused by long photoperiod is still unclear. This study investigated the anti-inflammatory effect of dietary tryptophan on intestinal inflammatory damage induced by long photoperiod and its potential mechanism in broiler chickens. We found that dietary tryptophan mitigated long photoperiod-induced intestinal tissue inflammatory damage and inhibited the activation of Nucleotide-Binding Oligomerization Domain, Leucine-Rich Repeat and Pyrin Domain-Containing 3 inflammasome. Moreover, dietary tryptophan significantly increased the relative abundance of Faecalibacterium, Enterococcus, and Lachnospiraceae_NC2004_group were significantly decreased the relative abundance of Ruminococcus_torques_group and norank_f_UCG-010 under the condition of long photoperiod (P < 0.05). The results of tryptophan targeted metabolomics show that tryptophan significantly increased indole-3-acetic acid (IAA) and indole-3 lactic acid (ILA), and significantly decreased xanthurenic acid (XA) under long photoperiod (P < 0.05). In conclusion, the results indicated that dietary tryptophan alleviates intestinal inflammatory damage caused by long photoperiod via the inhibition of Nucleotide-Binding Oligomerization Domain, Leucine-Rich Repeat and Pyrin Domain-Containing 3 inflammasome activation, which was mediated by tryptophan metabolites. Therefore, tryptophan supplementation could be a promising way to protect the intestine health under the condition of long photoperiod.PMID:38387289 | DOI:10.1016/j.psj.2024.103509

Taohe Chengqi decoction alleviated metabolic-associated fatty liver disease by boosting branched chain amino acids catabolism in the skeletal muscles of type 2 diabetes mellitus

Thu, 22/02/2024 - 12:00
Phytomedicine. 2023 Dec 25;126:155315. doi: 10.1016/j.phymed.2023.155315. Online ahead of print.ABSTRACTOBJECTIVE: Metabolic-associated fatty liver disease (MAFLD) is the most prevalent liver disease, whereas type 2 diabetes mellitus (T2DM) is considered an independent risk factor for MAFLD incidence. Taohe Chengqi decoction (THCQ) is clinically prescribed for T2DM treatment; however, the hepatoprotective effect of THCQ against MAFLD is still unknown. This study intended to elucidate the therapeutic effect of THCQ on T2DM-associated MAFLD and to investigate the underlying mechanisms.METHODS: THCQ lyophilized powder was prepared and analyzed by UHPLC-MS/MS. A stable T2DM mouse model was established by high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection. The T2DM mice were administered THCQ (2.5 g/kg or 5 g/kg) to explore the pharmacological effects of THCQ on T2DM-associated MAFLD. Liver tissue transcriptome was analyzed and the participatory roles of PPARα/γ pathways were verified both in vivo and in vitro. Serum metabolome analysis was used to explore the metabolome changes and skeletal muscle branched chain amino acid (BCAA) catabolic enzymes were further detected. Moreover, an AAV carrying BCKDHA shRNA was intramuscularly injected to verify the impact of THCQ on skeletal muscle BCAA catabolism and the potential therapeutic outcome on hepatic steatosis.RESULTS: THCQ improved hepatic steatosis in MAFLD. RNA-sequencing analysis showed dysregulation in the hepatic PPARγ-related fatty acid synthesis, while PPARα-dependent fatty acid oxidation was elevated following THCQ treatment. Interestingly, in vitro analyses of these findings showed that THCQ had minor effects on fatty acid oxidation and/or synthesis. The metabolomic study revealed that THCQ accelerated BCAA catabolism in the skeletal muscles, in which knockdown of the BCAA catabolic enzyme BCKDHA diminished the THCQ therapeutic effect on hepatic steatosis.CONCLUSION: This study highlighted the potential therapeutic effect of THCQ on hepatic steatosis in MALFD. THCQ upregulated fatty acid oxidation and reduced its synthesis via restoration of PPARα/γ pathways in HFD/STZ-induced T2DM mice, which is mediated through augmenting BCKDH activity and accelerating BCAA catabolism in the skeletal muscles. Overall, this study provided in-depth clues for "skeletal muscles-liver communication" in the therapeutic effect of THCQ against hepatic steatosis. These findings suggested THCQ might be a potential candidate against T2DM-associated MAFLD.PMID:38387274 | DOI:10.1016/j.phymed.2023.155315

Targeted arginine metabolomics combined with metagenomics revealed the potential mechanism of Pueraria lobata extract in treating myocardial infarction

Thu, 22/02/2024 - 12:00
J Chromatogr A. 2024 Feb 10;1719:464732. doi: 10.1016/j.chroma.2024.464732. Online ahead of print.ABSTRACTThe extraction methods for traditional Chinese medicine (TCM) may have varying therapeutic effects on diseases. Currently, Pueraria lobata (PL) is mostly extracted with ethanol, but decoction, as a TCM extraction method, is not widely adopted. In this study, we present a strategy that integrates targeted metabolomics, 16 s rDNA sequencing technology and metagenomics for exploring the potential mechanism of the water extract of PL (PLE) in treating myocardial infarction (MI). Using advanced analytical techniques like ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we comprehensively characterized PLE's chemical composition. Further, we tested its efficacy in a rat model of MI induced by ligation of the left anterior descending branch of the coronary artery (LAD). We assessed cardiac enzyme levels and conducted echocardiograms. UPLC-MS/MS was used to compare amino acid differences in serum. Furthermore, we investigated fecal samples using 16S rDNA sequencing and metagenomic sequencing to study intestinal flora diversity and function. This study demonstrated PLE's effectiveness in reducing cardiac injury in LAD-ligated rats. Amino acid metabolomics revealed significant improvements in serum levels of arginine, citrulline, proline, ornithine, creatine, creatinine, and sarcosine in MI rats, which are key compounds in the arginine metabolism pathway. Enzyme-linked immunosorbent assay (ELISA) results showed that PLE significantly improved arginase (Arg), nitric oxide synthase (NOS), and creatine kinase (CK) contents in the liver tissue of MI rats. 16 s rDNA and metagenome sequencing revealed that PLE significantly improved intestinal flora imbalance in MI rats, particularly in taxa such as Tuzzerella, Desulfovibrio, Fournierella, Oscillibater, Harryflintia, and Holdemania. PLE also improved the arginine metabolic pathway in the intestinal microorganisms of MI rats. The findings indicate that PLE effectively modulates MI-induced arginine levels and restores intestinal flora balance. This study, the first to explore the mechanism of action of PLE in MI treatment considering amino acid metabolism and intestinal flora, expands our understanding of the potential of PL in MI treatment. It offers fresh insights into the mechanisms of PL, guiding further research and development of PL-based medicines.PMID:38387153 | DOI:10.1016/j.chroma.2024.464732

Nontargeted metabolomics and enzyme inhibitory and antioxidant activities for chemical and biological characterization of jujube (Ziziphus jujuba) extracts

Thu, 22/02/2024 - 12:00
J Pharm Biomed Anal. 2024 Feb 15;242:116040. doi: 10.1016/j.jpba.2024.116040. Online ahead of print.ABSTRACTThe chemical and biologically active characterization of jujube samples (fruits, cores, and leaves) were carried out by the integrated nontargeted metabolomics and bioassay. Firstly, collision cross-section values of active compounds in jujubes were determined by ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Then, a multidimensional statistical analysis that contained principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis was employed to effectively cluster different tissues and types of jujubes, making identification more scientific. Furthermore, angiotensin-converting enzyme (ACE) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the quality of jujubes from a double activity dimension. The analytical results obtained by using ACE and DPPH to evaluate the quality of jujube were different from multivariate statistics, providing a reference for the application of jujube. Therefore, integrating chemical and biological perspectives to evaluate the quality of jujube provided a more comprehensive evaluation and effective reference for clinical needs.PMID:38387129 | DOI:10.1016/j.jpba.2024.116040

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