PubMed

Exp Dermatol. 2024 Aug;33(8):e15165. doi: 10.1111/exd.15165.ABSTRACTPhenylalanine is a crucial amino acid in the process of melanogenesis. However, the exact mechanism by which it is transported into melanocytes has not been disclosed. The aim of this study was to identify and examine the key transporters that are responsible for phenylalanine transportation and evaluate their significance in melanogenesis. The amino acid transporter SLC16A10 was found to be up-regulated in both melasma (GSE72140) and sun-exposed skin (GSE67098). The protein levels of SLC16A10 were proportional to the melanin content in melanocytic nevi, indicating that SLC16A10 was related to melanogenesis. After SLC16A10 overexpression, melanin increased significantly in MNT1 cells. Meanwhile, the expression of melanogenesis-related proteins such as TYR and TYRP1 increased, while their RNA levels did not change. Transcriptomics data indicated that SLC16A10 can enhance the function of ribosome. Furthermore, targeted metabolomics data and ELISA results demonstrated SLC16A10 mainly affected the transport of phenylalanine into the cells. Then, phenylalanine was added to the cell culture medium after SLC16A10 overexpression, melanin synthesis in cells furtherly increased, which verified that SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine. Finally, we found that SLC16A10 expression increased after UVB irradiation. Knockdown SLC16A10 reduced UVB-induced melanin production and phenylalanine uptake by cells. In summary, SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine, and upregulation SLC16A10 is likely responsible for the UVB-induced hyperpigmentation as well.PMID:39171634 | DOI:10.1111/exd.15165

Food Funct. 2024 Aug 22. doi: 10.1039/d4fo02233e. Online ahead of print.ABSTRACTThe main constituents of saffron are the apocarotenoids crocins and crocetin, present in the stigmas. Numerous healthy properties, especially those related to the effects on the central nervous system, have been attributed to these compounds but the metabolites responsible for these effects are still unknown. Previous evidences in animal models suggest a role for the gut microbiota in the pharmacokinetics and the neuroprotective effects of these compounds. However, the interaction between these apocarotenoids and the gut microbiota has been poorly studied. In this article, we have thoroughly investigated the batch fermentation of crocin-1 and crocetin (10 μM) with human fecal samples of two donors at different incubation times (0-240 h) using a metabolomic approach. We corroborated a rapid transformation of crocin-1 which looses the glucose molecules through de-glycosylation reactions until its complete transformation into crocetin in 6 hours. A group of intermediate crocins with different degrees of glycosylation were detected in a very short time. Crocetin was further metabolized and new microbial metabolites produced by double-bond reduction and demethylation reactions were identified for the first time: dihydro and tetrahydro crocetins and di-demethyl crocetin. In addition, we detected changes in the levels of the short chain fatty acids valeric acid and hexanoic acid suggesting further structural modifications of crocetin or changes in the catabolic production of these compounds. This research is a pioneering study of the action of the human gut microbiota on the saffron apocarotenoids and goes one step further towards the discovery of metabolites potentially involved in the benefits of saffron.PMID:39171480 | DOI:10.1039/d4fo02233e

J Sci Food Agric. 2024 Aug 22. doi: 10.1002/jsfa.13832. Online ahead of print.ABSTRACTBACKGROUND: Genetic breeding is essential to develop grapevine genotypes adapted to warm climates and resistant to pathogens. Traditionally cultivated Vitis vinifera is susceptible to biotic and abiotic stresses. Winemakers and consumers, however, perceive wines from non-vinifera or hybrid cultivars as inferior. In this study, sensory analyses and comprehensive metabolite profiling by targeted and untargeted approaches were used to investigate the oenological potential of wines from grapes of genotypes developed throughout four breeding cycles to improve climate adaptation, sugar contents and berry color.RESULTS: Novel genotypes had higher yields and the wines exhibited increased contents of polyphenols, including anthocyanins. Volatile monoterpenes in the wines decreased throughout breeding cycles in the absence of selective pressure. Polyphenol contents were higher in intermediate wines, with hydroxytyrosol contents reaching up to three times reported values. Mouthfeel attributes astringency, leafy taste, flavor and body, and persistency showed significant correlation with untargeted features. Supervised model-based analyses of the metabolome effectively discriminate wines from distinct genetic origins.CONCLUSION: Taken together, the results demonstrate the potential of novel grapevine genotypes to a more sustainable viticulture and quality wine production in warm climates. Comprehensive metabolite profiling of the wines reveals that genotype clustering is dependent on the chemical class and that traits not submitted to selective pressure are also altered by breeding. Supervised multivariate models were effective to predict the genetic origin of the wines based on the metabolic profile, indicating the potential of the technique to identify biomarkers for wines from sustainable genotypes. © 2024 Society of Chemical Industry.PMID:39171419 | DOI:10.1002/jsfa.13832

Front Public Health. 2024 Aug 7;12:1386441. doi: 10.3389/fpubh.2024.1386441. eCollection 2024.ABSTRACTINTRODUCTION: Metal carpentry includes a wide range of work activities such as welding and cutting metallic components, use of solvents and paints. Therefore, the employees in these types of activities are mainly exposed to welding fumes and volatile organic solvents. Here, we present an NMR-based metabolomic approach for assessing urinary profiles of workers in the same company that are exposed to two different risk factors.METHODS: The study enrolled 40 male subjects exposed to welding fumes, 13 male subjects exposed to volatile organic compounds of a metal carpentry company, and 24 healthy volunteers. All samples were collected, in the middle of the working week at fast. Thirty-five urinary metabolites belonging to different chemical classes such as amino acids, organic acids and amines were identified and quantified. Results were processed by multivariate statistical analysis for identifying significant metabolites for each working group examined, compared to controls.RESULTS: Workers exposed to welding fumes displayed urinary increase in glutamine, tyrosine, taurine, creatine, methylguanidine and pseudouridine associated to oxidative impairment, while workers exposed to volatile organic compounds showed higher urinary levels of branched chain aminoacids.CONCLUSION: Our work identified specific urinary profile related to each occupational exposure, even if it is below the threshold limit values.PMID:39171307 | PMC:PMC11335539 | DOI:10.3389/fpubh.2024.1386441

Chin Med J Pulm Crit Care Med. 2023 Dec 8;1(4):223-230. doi: 10.1016/j.pccm.2023.10.001. eCollection 2023 Dec.ABSTRACTChronic obstructive pulmonary disease (COPD) is a chronic lung disease with limited airflow. COPD is characterized by chronic bronchitis and emphysema, and is often accompanied by malnutrition with fatigue, muscle weakness, and an increased risk of infection. Although the pulmonary function test is used as the gold criterion for diagnosing COPD, it is unable to identify early COPD or classify the subtypes, thereby impeding early intervention and the precise diagnosis of COPD. Recent evidence suggests that metabolic dysfunction, such as changes in lipids, amino acids, glucose, nucleotides, and microbial metabolites in the lungs and intestine, have a great potential for diagnosing COPD in the early stage. However, a comprehensive summary of these metabolites and their effects on COPD is still lacking. This review summarizes the metabolites that are changed in COPD and highlights some promising early diagnostic markers and therapeutic targets. We emphasize that intensified dietary management may be among the most feasible methods to improve metabolism in the body.PMID:39171278 | PMC:PMC11332835 | DOI:10.1016/j.pccm.2023.10.001

Int J Cardiol Heart Vasc. 2024 Jul 30;54:101477. doi: 10.1016/j.ijcha.2024.101477. eCollection 2024 Oct.ABSTRACTSepsis-induced cardiomyopathy (SIC) is a common and high-mortality complication among critically ill patients. Uncertainties persist regarding the pathogenesis, pathophysiology, and diagnosis of SIC, underscoring the necessity to investigate potential biological mechanisms. With the rise of omics technologies, leveraging their high throughput and big data advantages, a systems biology perspective is employed to study the biological processes of SIC. This approach aids in gaining a better understanding of the disease's onset, progression, and outcomes, ultimately providing improved guidance for clinical practices. This review summarizes the currently applied omics technologies, omics studies related to SIC, and relevant omics databases.PMID:39171080 | PMC:PMC11334652 | DOI:10.1016/j.ijcha.2024.101477

Front Plant Sci. 2024 Aug 7;15:1447860. doi: 10.3389/fpls.2024.1447860. eCollection 2024.ABSTRACTINTRODUCTION: Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. cucumerinum (Foc) is a destructive soil-borne disease in cucumber (Cucumis sativus. L). However, there remains limited knowledge on the molecular mechanisms underlying FW resistance-mediated defense responses in cucumber.METHODS: In this study, metabolome and transcriptome profiling were carried out for two FW resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. NILs have shown consistent and stable resistance in multiple resistance tests conducted in the greenhouse and in the laboratory. A widely targeted metabolomic analysis identified differentially accumulated metabolites (DAMs) with significantly greater NR accumulation in response to Foc infection, including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway.RESULTS: Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis and transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with the biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NR-conferred FW resistance was exemplified by in vivo assays. These assays found two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, as well as the flavonoid compound gallocatechin 3-O-gallate to have significant inhibitory effects on Foc growth. The antifungal effects of these three compounds represent a novel finding.DISCUSSION: Therefore, phenolic acids and flavonoids play important roles in NR mediated FW resistance breeding in cucumber.PMID:39170788 | PMC:PMC11335689 | DOI:10.3389/fpls.2024.1447860

ACS Food Sci Technol. 2024 Jul 22;4(8):1937-1949. doi: 10.1021/acsfoodscitech.4c00298. eCollection 2024 Aug 16.ABSTRACTWe report the development of MagMet-W (magnetic resonance for metabolomics of wine), a software program that can automatically determine the chemical composition of wine via 1H nuclear magnetic resonance (NMR) spectroscopy. MagMet-W is an extension of MagMet developed for the automated metabolomic analysis of human serum by 1H NMR. We identified 70 compounds suitable for inclusion into MagMet-W. We then obtained 1D 1H NMR reference spectra of the pure compounds at 700 MHz and incorporated these spectra into the MagMet-W compound library. The processing of the wine NMR spectra and profiling of the 70 wine compounds were then optimized based on manual 1H NMR analysis. MagMet-W can automatically identify 70 wine compounds in most wine samples and can quantify them to 10-15% of the manually determined concentrations, and it can analyze multiple spectra simultaneously, at 10 min per spectrum. The MagMet-W Web server is available at https://www.magmet.ca.PMID:39170760 | PMC:PMC11334181 | DOI:10.1021/acsfoodscitech.4c00298

Front Vet Sci. 2024 Aug 7;11:1411520. doi: 10.3389/fvets.2024.1411520. eCollection 2024.ABSTRACTINTRODUCTION: Despite the absence of definitive evidence indicating that the cp4-epsps gene and its resultant recombinant proteins have significant harmful effects on either human or animal health, the safety assessment of genetically modified (GM) crops expressing the CP4-EPSPS proteins has been controversial. This study endeavor was aimed at evaluating the potential risks posed by the CP4-EPSPS protein in transgenic crops, thereby contributing to the advancement of risk assessment methodologies in the context of genetically engineered crops.METHODS: To ascertain the appropriate daily dosages for oral gavage administration, the expression levels of the CP4-EPSPS protein in a recombinant yeast were quantified. Subsequently, physiological and biochemical analysis, metabolomics, and metagenomic analysis were conducted based on a 90-day Sprague-Dawley (SD) rats feeding experiment, respectively, thereby enhancing the depth and precision of our risk assessment framework.RESULTS: The results from the physiological and biochemical analysis, organ pathological, blood metabolism, gut microbiota, and correlation analysis of metabolites and gut microbiota revealed several biomarkers for further risk assessment. These biomarkers include clinical biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), creatine kinase (CK), and lactate dehydrogenase (LDH); metabolites like Methionine, 2-Oxovaleric acid, and LysoPC (16:0); and gut microbiota including Blautia wexlerae, Holdemanella biformis, Dorea sp. CAG 317, Coriobacteriaceae and Erysipelotrichaceae.CONCLUSION: In conclusion, the risk can be significantly reduced by directly consuming inactivated recombinant CP4-EPSPS. Therefore, in everyday life, the risk associated with consuming GM foods containing recombinant CP4-EPSPS is substantially reduced after heat treatment.PMID:39170628 | PMC:PMC11335726 | DOI:10.3389/fvets.2024.1411520

Heliyon. 2024 Aug 5;10(15):e35491. doi: 10.1016/j.heliyon.2024.e35491. eCollection 2024 Aug 15.ABSTRACTAs a classical traditional Chinese patent medicine, Shugan Yipi Granule is widely used in China to treat non-alcoholic fatty liver disease (NAFLD) recently. Our previous study confirmed that Shugan Yipi Granule are effective in NAFLD. However, its underlying mechanism is still unknown. This study aims to investigate the mechanism of Shugan Yipi Granule on NAFLD based on network pharmacology prediction, liquid chromatography-mass spectrometry (LC-MS) analysis and in vitro verification. We obtained the active ingredients and targets of Shugan Yipi Granule and NAFLD from 6 traditional Chinese medicine databases, and the crucial components and targets screened by protein-protein interaction (PPI) network were used for molecular docking. Plasma metabolomics of NAFLD patients treated with Shugan Yipi Granule for one month was analyzed using LC-MS methods and MetaboAnalyst 4.0 to obtain significant differential metabolites and pathways. Finally, free fatty acid (FFA) induced HepG2 cells were treated with different concentrations of quercetin and kaempferol, then oil red o (ORO) and triglyceride (TG) level were tested to verify the lipid deposition of the cell. Network pharmacology analysis showed that the main active ingredients of Shugan Yipi Granule include quercetin, kaempferol and other 58 ones, as well as 188 potential targets. PI3K/Akt signaling pathway was found to be the most relevant pathway for the treatment of NAFLD. Non-targeted metabolomics showed that quercetin and kaempferol were significantly up-regulated differential metabolites and were involved in metabolic pathways such as thyroid hormone signaling. In vitro results showed that quercetin, kaempferol were effective in reducing lipid deposition and TG content by inhibiting cellular fatty acid uptake. Ultimately, with the network pharmacology and serum metabolomics analysis, quercetin and kaempferol were found to be the important active ingredients and significantly up-regulated differential metabolites of Shugan Yipi Granule against NAFLD, which we inferred that they may regulate NAFLD through PI3K/Akt signaling pathway and thyroid hormone metabolism pathway. The in vitro experiment verification results showed that quercetin and kaempferol attenuated the lipid accumulation and TG content by inhibiting the fatty acid uptake in the FFA-induced HepG2 cell. Current study provides the necessary experimental basis for subsequent in-depth mechanism research.PMID:39170438 | PMC:PMC11336705 | DOI:10.1016/j.heliyon.2024.e35491

Heliyon. 2024 Jul 30;10(15):e35443. doi: 10.1016/j.heliyon.2024.e35443. eCollection 2024 Aug 15.ABSTRACTCOVID-19 is a highly contagious infectious disease that has posed a global threat, leading to a widespread pandemic characterized by multi-organ complications and failures.AIMS: The present study was conducted to evaluate the impact of Pfizer and Sinopharm vaccines on metabolomic changes and their correlations with immune pathways.MAIN METHODS: The study used a cross-sectional design and implemented an untargeted metabolomics-based approach. Plasma samples were obtained from three groups: non-vaccinated participants, Sinopharm-vaccinated participants, and Pfizer-vaccinated participants. Comparative metabolomic analysis was conducted using TIMS-QTOF, and multiple t-tests with a 5 % false discovery rate (FDR) were performed using MetaboAnalyst software.KEY FINDINGS: Out of the 105 metabolites detected, 72 showed statistically significant changes (p-value < 0.05) across the different groups. Notably, several metabolites such as neopterin, pyridoxal, and syringic acid were markedly altered in individuals vaccinated with Pfizer. Conversely, in the Sinopharm-vaccinated group, significant alterations were observed in sphinganine, neopterin, and sphingosine. These metabolites hold potential as biomarkers for evaluating vaccine efficacy. Additionally, both Pfizer and Sinopharm vaccinations were found to influence sphingolipid and histidine metabolisms compared to the control group. The Sinopharm group also displayed changes in lysine degradation relative to the control group. When comparing the enriched pathways between the Pfizer and Sinopharm-vaccinated groups, differences were observed in purine metabolism. Furthermore, alterations in tryptophan and vitamin B6 metabolism were noted when comparing the Pfizer-vaccinated group with both the control and Sinopharm-vaccinated groups.SIGNIFICANCE: These findings highlight the importance of metabolomics in assessing vaccine effectiveness and identifying potential biomarkers for monitoring the efficacy of newly developed vaccines in a shorter timeframe.PMID:39170395 | PMC:PMC11336712 | DOI:10.1016/j.heliyon.2024.e35443

Heliyon. 2024 Jul 20;10(15):e34917. doi: 10.1016/j.heliyon.2024.e34917. eCollection 2024 Aug 15.ABSTRACTBACKGROUND: This study aimed to investigate the effect of eight weeks of high-intensity interval training (HIIT) on muscle metabolism in rats with type 2 diabetes (T2D) using metabolomics approaches.METHODS: 20 male Wistar rats at the age of 8 weeks-were assigned to four groups of five, each in the group randomly: control (CTL), type 2 diabetes (DB), HIIT (EX), and type 2 diabetes + HIIT (DBX). T2D was induced by two months of a high-fat diet plus a single dose of streptozotocin (35 mg/kg). Rats in the EX and DBX groups performed eight weeks of HIIT (running at 80-100 % of Vmax, 4-10 intervals). NMR spectroscopy was used to determine the changes in the muscle metabolome profile after training.RESULTS: Changes in metabolite abundance following exercise revealed distinct clustering in multivariate analysis. The essential metabolite changes between the DB and CTL groups were arginine metabolism, purine metabolism, phosphate pathway, amino sugar metabolism, glutathione metabolism, and aminoacyl-tRNA biosynthesis. However, Arginine biosynthesis, pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism were altered between the DBX and DB groups.CONCLUSION: These results suggest that eight weeks of HIIT could reverse metabolic changes induced by T2D in rat muscles, contributing to reduced FBG and HOMA-IR levels.PMID:39170342 | PMC:PMC11336285 | DOI:10.1016/j.heliyon.2024.e34917

Heliyon. 2024 Aug 3;10(15):e35755. doi: 10.1016/j.heliyon.2024.e35755. eCollection 2024 Aug 15.ABSTRACTIntestinal flora metabolites played a crucial role in immunomodulation by influencing host immune responses through various pathways. Macrophages, as a type of innate immune cell, were essential in chemotaxis, phagocytosis, inflammatory responses, and microbial elimination. Different macrophage phenotypes had distinct biological functions, regulated by diverse factors and mechanisms. Advances in intestinal flora sequencing and metabolomics have enhanced understanding of how intestinal flora metabolites affect macrophage phenotypes and functions. These metabolites had varying effects on macrophage polarization and different mechanisms of influence. This study summarized the impact of gut microbiota metabolites on macrophage phenotype and function, along with the underlying mechanisms associated with different metabolites produced by intestinal flora.PMID:39170251 | PMC:PMC11337042 | DOI:10.1016/j.heliyon.2024.e35755

Heliyon. 2024 Aug 6;10(15):e35861. doi: 10.1016/j.heliyon.2024.e35861. eCollection 2024 Aug 15.ABSTRACTThe issue of non-renewable energy scarcity has persisted over an extended period, primarily due to the depletion of fossil fuel reserves and the adverse effects of their utilization. This scarcity stems from the finite nature of fossil energy resources. The development of oil energy or biofuels aims to utilize oil-producing plants such as Jatropha curcas to develop alternative energy resources. However, metabolomic studies in Jatropha curcas are limited and need more investigations. Therefore, this research was essential to find biomarkers of metabolites among the fruit, leaf, and stem of Jatropha curcas using the GC-MS technique. We tested the metabolite profile with the R program, especially the metaboanalystR package, to determine fold change metabolite and pathway analysis. We found that 54 metabolites were detected in both fruit, leaf, and stem tissues of Jatropha curcas L, of which 19 metabolites were upregulated in the fruit, 20 metabolites in the leaf, and 15 up-regulated metabolites in the stem. The metabolites found formed three clusters based on correlation and networking metabolites analysis. The three clusters showed a relationship with the lipid biosynthesis pathway. In this study, provisional information was obtained that there was a different pattern of expression of metabolites between fruit, leaf, and stem tissues in Jatropha curcas, which was thought to be related to the critical metabolites of oleic acid and methylcyclohexane carboxylate in the biosynthetic pathway of fatty acids and unsaturated fatty acids. This information is essential as an initial reference for genetic engineering Jatropha curcas so that it can be used to transform plants, especially lipid-producing plants, as a source of oil.PMID:39170246 | PMC:PMC11337045 | DOI:10.1016/j.heliyon.2024.e35861

Heliyon. 2024 Jul 30;10(15):e35394. doi: 10.1016/j.heliyon.2024.e35394. eCollection 2024 Aug 15.ABSTRACTPolygonati Rhizoma (PR, Huangjing in Chinese) and its processed product (PRP), which are used in Traditional Chinese medicine (TCM) for cognitive enhancement and treatment of Alzheimer's disease (AD), have not been fully explored in terms of the different mechanisms underlying their anti-AD effects. Therefore, we used APP/PS1 mice as an AD model to assess the effects of PR and PRP on anxiety-like behaviors, cognitive function, memory performance, and pathological changes in the murine brain. UPLC-HRMS was applied to identify the components of PR and PRP that entered into the blood and brain. Network pharmacology was used to elucidate potential mechanisms underlying the improvement of AD. Differences in the intestinal flora composition between mice treated with PR and PRP were investigated using 16S rRNA sequencing, establishing a correlation between pharmacological components and distinct flora profiles. The results revealed that both PR and PRP interventions ameliorated cognitive deficits and attenuated Amyloid β (Aβ) plaque deposition in the brains of AD mice. Seven specific blood-entering components, namely glutamic acid, Phe-Phe, and uridine, etc., were associated with PR intervention, whereas ten specific blood-entering components including (2R,3S)-3-isopropylmalate, 3-methylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione, and 3-methoxytyrosine were related to PRP intervention. Uridine was identified as a common brain-penetrating component in both PR and PRP interventions. Network pharmacology analysis suggested that the NOD-like receptor signaling pathway, Calcium signaling pathway and Alzheimer's disease were specific pathways targeted in AD treatment using PR intervention. Moreover, the apoptosis pathway was specifically linked to AD treatment during PRP intervention. Furthermore, the administration of both PR and PRP enhanced the abundance and diversity of the intestinal flora in APP/PS1 mice. Western blotting confirmed that PR excels in regulates inflammation, whereas PRP balances autophagy and apoptosis to alleviate the progression of AD. This study offers valuable insights and establishes a robust foundation for further comprehensive exploration of the intrinsic correlation between TCM and AD.PMID:39170207 | PMC:PMC11336570 | DOI:10.1016/j.heliyon.2024.e35394

Heliyon. 2024 Jul 9;10(15):e34317. doi: 10.1016/j.heliyon.2024.e34317. eCollection 2024 Aug 15.ABSTRACTBACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world. It has become increasingly difficult to meet the needs of precision therapy using the existing molecular typing system. Therefore, developing a more effective molecular typing system for GC is urgent.METHODS: In this study, 100 Chinese GC patients were included. Whole-exome sequencing (WES) and metabolomics analysis were performed to reveal the characteristics of genomic and metabolic changes.RESULTS: In WES, nonsynonymous mutations accounted for the majority. Based on metabolomics, GC has been divided into three subtypes with distinct metabolic features. Importantly, we ultimately divided GC into four subtypes with different metabolic characteristics, genomic alterations, and clinical prognoses by incorporating biomics analysis.CONCLUSIONS: Integrating biological features, we constructed a novel molecular system for GC that was closely related to genetics and metabolism, providing new insights for further understanding the heterogeneity and formulating precise treatment strategies.PMID:39170180 | PMC:PMC11336309 | DOI:10.1016/j.heliyon.2024.e34317

Phytochem Anal. 2024 Aug 21. doi: 10.1002/pca.3436. Online ahead of print.ABSTRACTINTRODUCTION: Cannabis sativa is a highly versatile plant with a long history of cultivation and domestication. It produces multiple compounds that exert distinct and valuable therapeutic effects by modulating diverse biological systems, including the endocannabinoid system (ECS). Access to standardized, metabolically diverse, and reproducible C. sativa chemotypes and chemovars is essential for physicians to optimize individualized patient treatment and for industries to conduct drug-discovery campaigns.OBJECTIVE: This study aimed to characterize and assess the phytochemical diversity of C. sativa chemotypes in diverse ecological regions of Colombia, South America.METHODOLOGY: Ten cannabinoids and 23 terpenes were measured using liquid and gas chromatography, in addition to other phenotypic traits, in 156 C. sativa plants that were grown in diverse ecological regions in Colombia, a hotspot for global biodiversity.RESULTS: Our results reveal significant phytochemical diversity in Colombian-grown C. sativa plants, with four distinct chemotypes based on cannabinoid profile. The significant amount of usually uncommon terpenes suggests that Colombia's environments may have unique capabilities that allow the plant to express these compounds. Colombia's diverse climates offer enormous cultivation potential, making it a key player in both domestic and international medicinal and recreational C. sativa trade.CONCLUSION: These findings underscore Colombia's capacity to pioneer global C. sativa production diversification, particularly in South America with new emerging markets.PMID:39169651 | DOI:10.1002/pca.3436

J Sep Sci. 2024 Aug;47(16):e2400436. doi: 10.1002/jssc.202400436.ABSTRACTSteroids can be used as biomarkers in clinical metabolomics and other fields related to human toxicology. This chemical group is known for its complexity, considering its number of isobaric compounds and the wide variety of phases I and II metabolic pathways that parent compounds can undergo. For a successful analysis of steroids in biological samples, liquid chromatography separation must be finely tuned. It is especially challenging for glucuronidated and sulfated steroids derivatives that bear polar heads and can be affected by non-specific adsorption. The benefits of a biphenyl stationary phase chemistry for the selectivity of the separation of steroids and their phase II metabolites and the extent to which nonspecific adsorption phenomena could degrade chromatographic performance were investigated. Replacing a conventional hardware by a passivated hardware allowed to considerably reduce peaks width and asymmetry of sulfated species. The addition of weak ion pairing agents in the mobile phase could also help to reduce non-specific adsorption but are detrimental to mass spectrometry detection. As confirmed by the successful detection of 52 steroids in plasma, the use of a biphenyl stationary phase complemented by a passivated column hardware is of great help for a successful biomedical analysis of steroids and their phase II metabolites.PMID:39169650 | DOI:10.1002/jssc.202400436

Arthritis Care Res (Hoboken). 2024 Aug 21. doi: 10.1002/acr.25420. Online ahead of print.ABSTRACTOBJECTIVES: Our objective was to prospectively investigate pre-diagnostic population-based metabolome for risk of hospitalized gout (i.e., most accurate, severe, and costly cases), accounting for serum urate.METHODS: We conducted pre-diagnostic metabolome-wide analyses among 249,677 UK Biobank participants with NMR metabolomic profiling (N=168 metabolites, including eight amino acids) from baseline blood samples (2006-2010), without a history of gout. We calculated multivariable hazard ratios (HRs) for incident hospitalized gout, before and after adjusting for serum urate levels; we included non-hospitalised incident gout cases in a sensitivity analysis. Potential causal effects were evaluated with two-sample Mendelian randomization.RESULTS: Correcting for multiple testing, 107 metabolites were associated with incidence of hospitalized gout (N=2735) before urate adjustment, including glycine and glutamine (inversely; HR=0.64 [95% CI: 0.54, 0.75], P=8.3x10-8 and HR=0.69 [0.61, 0.78], P=3.3x10-9 between extreme quintiles, respectively), and glycoprotein acetyls (GlycA; HR=2.48 [2.15, 2.87], P=1.96x10-34). Associations remained significant and directionally-consistent following urate adjustment (HR=0.83 [0.70, 0.98], 0.86 [0.76, 0.98], 1.41 [1.21, 1.63] between extreme quintiles), respectively; corresponding HR per SD were 0.91 (0.86, 0.97), 0.94 (0.91, 0.98), and 1.10 (1.06, 1.14). Findings persisted when including non-hospitalised incident gout cases. Mendelian randomization corroborated their potential causal role on hyperuricemia or gout risk; with change in urate levels of -0.05 mg/dL (-0.08, -0.01), and -0.12 mg/dL (-0.22, -0.03), per SD of glycine and glutamine, respectively, and ORs 0.94 (0.88, 1.00), and 0.81 (0.67, 0.97), for gout.CONCLUSION: These prospective findings with causal implications could lead to biomarker-based risk prediction and potential supplementation-based interventions with glycine or glutamine.PMID:39169570 | DOI:10.1002/acr.25420

Bioresour Technol. 2024 Aug 19:131312. doi: 10.1016/j.biortech.2024.131312. Online ahead of print.ABSTRACTMicrobial oils have been of considerable interest as food additives and biofuel resources due to high lipid contents, but lipid accumulation of oleaginous microorganisms can be induced by environmental stresses, such as dissolved oxygen (DO), which limit large-scale lipid production. Here, DO stress gave rise to the endogenous nitric oxide (NO) level to mediate S-nitrosylation of SpAsg1, regulating the lipid accumulation in Saitozyma podzolica zwy-2-3. Notably, qRT-PCR, yeast one-hybrid, dual-luciferase reporter assays, and metabolomics analysis exhibited that overexpression of SpAsg1 promoted lipid synthesis by directly regulation of glucose metabolism, enhancing glucose uptake, ATP and NADPH contents under DO stress. Meanwhile, SpAsg1 improved the antioxidant capacity to reduce the intracellular reactive oxygen species (ROS) and NO levels. Overall, we systematically investigated the regulation of SpAsg1 on lipid metabolism of S. podzolica zwy-2-3 under DO stress, which sheds light on further studies for alleviating oxygen limitation of lipid production in microbial industry.PMID:39168414 | DOI:10.1016/j.biortech.2024.131312