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

Investigating the impact of pedoclimatic conditions on the oenological performance of two red cultivars grown throughout southern Italy

Mon, 02/10/2023 - 12:00
Front Plant Sci. 2023 Sep 15;14:1250208. doi: 10.3389/fpls.2023.1250208. eCollection 2023.ABSTRACTThe cultivated grapevine, Vitis vinifera subsp. vinifera, possesses a rich biodiversity with numerous varieties. Each variety adapts differently to varying pedoclimatic conditions, which greatly influence the terroir expression of wine regions. These conditions impact vine growth, physiology, and berry composition, ultimately shaping the unique characteristics and typicity of the wines produced. Nowadays, the potential of the different adaptation capacities of grape varieties has not yet been thoroughly investigated. We addressed this issue by studying two grape varieties, Aglianico and Cabernet Sauvignon, in two different pedoclimatic conditions of Southern Italy. We evaluated and compared the effect of different pedoclimatic conditions on plant physiology, the microbial quality of grapes using Next-Generation Sequencing (NGS) technology, the expression trends of key genes in ripe berries and the concentration of phenolic compounds in grapes and wines by HPLC-MS, HPLC-DAD, NMR and spectrophotometric analyses. Metabolomic and microbiome data were integrated with quantitative gene expression analyses to examine varietal differences and plasticity of genes involved in important oenological pathways. The data collected showed that the phenotypic response of studied grapes in terms of vigor, production, and fruit quality is strongly influenced by the pedoclimatic conditions and, in particular, by soil physical properties. Furthermore, Aglianico grape variety was more influenced than the Cabernet Sauvignon by environmental conditions. In conclusion, the obtained findings not only reinforce the terroir concept and our comprehension of grape's ability to adapt to climate variations but can also have implications for the future usage of grape genetic resources.PMID:37780525 | PMC:PMC10540683 | DOI:10.3389/fpls.2023.1250208

Analysis of the effect of different withering methods on tea quality based on transcriptomics and metabolomics

Mon, 02/10/2023 - 12:00
Front Plant Sci. 2023 Sep 14;14:1235687. doi: 10.3389/fpls.2023.1235687. eCollection 2023.ABSTRACTWithering is very important to the quality of Wuyi rock tea. In this study, transcriptomics and metabolomics were used to analyze the effects of different withering methods on tea quality formation. The results showed that sunlight withering (SW) was most beneficial in increasing the gene expression of ubiquinone and other terpenoid-quinone biosynthesis (ko00130), pyruvate metabolism (ko00620), starch and sucrose metabolism (ko00500), and tryptophan metabolism (ko00380) pathways, and increasing the content of nucleotides and derivatives, terpenoids, organic acids and lipids, thus enhancing the mellowness, fresh and brisk taste and aroma of tea. Withering trough withering (WW) was most beneficial in increasing the gene expression of glutathione metabolism (ko00480), phenylpropanoid biosynthesis (ko00940) pathways, increasing the content of phenolic acids and flavonoids, thus enhancing tea bitterness. A comprehensive evaluation of the metabolite content and taste characteristics of tea leaves showed SW to be the best quality and charcoal fire withering (FW) to be the worst quality. This study provided an important basis for guiding the processing of Wuyi rock tea with different flavors.PMID:37780509 | PMC:PMC10538532 | DOI:10.3389/fpls.2023.1235687

Integrated analysis of transcriptome, metabolome, and histochemistry reveals the response mechanisms of different ages <em>Panax notoginseng</em> to root-knot nematode infection

Mon, 02/10/2023 - 12:00
Front Plant Sci. 2023 Sep 14;14:1258316. doi: 10.3389/fpls.2023.1258316. eCollection 2023.ABSTRACTPanax notoginseng (P. notoginseng) is an invaluable perennial medicinal herb. However, the roots of P. notoginseng are frequently subjected to severe damage caused by root-knot nematode (RKN) infestation. Although we have observed that P. notoginseng possessed adult-plant resistance (APR) against RKN disease, the defense response mechanisms against RKN disease in different age groups of P. notoginseng remain unexplored. We aimed to elucidate the response mechanisms of P. notoginseng at different stages of development to RKN infection by employing transcriptome, metabolome, and histochemistry analyses. Our findings indicated that distinct age groups of P. notoginseng may activate the phenylpropanoid and flavonoid biosynthesis pathways in varying ways, leading to the synthesis of phenolics, flavonoids, lignin, and anthocyanin pigments as both the response and defense mechanism against RKN attacks. Specifically, one-year-old P. notoginseng exhibited resistance to RKN through the upregulation of 5-O-p-coumaroylquinic acid and key genes involved in monolignol biosynthesis, such as PAL, CCR, CYP73A, CYP98A, POD, and CAD. Moreover, two-year-old P. notoginseng enhanced the resistance by depleting chlorogenic acid and downregulating most genes associated with monolignol biosynthesis, while concurrently increasing cyanidin and ANR in flavonoid biosynthesis. Three-year-old P. notoginseng reinforced its resistance by significantly increasing five phenolic acids related to monolignol biosynthesis, namely p-coumaric acid, chlorogenic acid, 1-O-sinapoyl-D-glucose, coniferyl alcohol, and ferulic acid. Notably, P. notoginseng can establish a lignin barrier that restricted RKN to the infection site. In summary, P. notoginseng exhibited a potential ability to impede the further propagation of RKN through the accumulation or depletion of the compounds relevant to resistance within the phenylpropanoid and flavonoid pathways, as well as the induction of lignification in tissue cells.PMID:37780502 | PMC:PMC10539906 | DOI:10.3389/fpls.2023.1258316

Non-targeted metabolomics characterization of flavor formation of Lichuan black tea processed from different cultivars in Enshi

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jul 23;19:100809. doi: 10.1016/j.fochx.2023.100809. eCollection 2023 Oct 30.ABSTRACTNine tea cultivars planted in Enshi were selected and processed into "Lichuan black tea". Sensory evaluation showed that cultivar had the greatest influence on taste and aroma quality, including sweetness, umami and concentration of taste, as well as sweet and floral fragrances of aroma. The non-volatile and volatile components were identified by UPLC-Q-TOF/MS and GC-MS, and PCA analysis showed good separation between cultivars, which could cause the difference in quality. Baiyaqilan, Meizhan and Echa 10 had a floral aroma, with obvious difference in their aromatic composition from other cultivars. Moreover, Echa 10 also had a strong sweet aroma. The key aroma components in Echa 10 (with the largest cultivation area) were further investigated by GC-O-MS combined with odor activity value (OAV) analysis, included β-damascenone, phenylethylaldehyde, nonenal, geraniol, linalool, jasmonone, (E)-2-nonenal, β-cyclocitral, (E)-β-ocimene, methyl salicylate, β-ionone, 2,6,10,10-tetramethyl-1-oxaspiro[4.5]dec-6-ene, citral, β-myrcene, nerol, phenethyl alcohol, benzaldehyde, hexanal, nonanoic acid, and jasmin lactone.PMID:37780350 | PMC:PMC10534183 | DOI:10.1016/j.fochx.2023.100809

UPLC-Q-TOF/MS-based metabonomics reveals mechanisms for <em>Holothuria leucospilota</em> polysaccharides (HLP)-regulated serum metabolic changes in diabetic rats

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jun 16;19:100741. doi: 10.1016/j.fochx.2023.100741. eCollection 2023 Oct 30.ABSTRACTThis study aimed to use metabolomic methods to explore how Holothuria leucospilota polysaccharides (HLP) improved metabolism disorders in the liver of Goto-Kakizaki (GK) rats with spontaneous type 2 diabetes. The results showed that HLP effectively improved the metabolic disorder. Based on KEGG functional analysis, five key biomarkers associated with bile acid metabolism were detected and screened (P < 0.05). The results of serum total bile acid levels and liver damage in diabetic rats further showed the regulatory effects of HLP on bile acid metabolism. The results of bile acid-related gene expression in the liver showed that HLP inhibited liver farnesoid X Receptor - small heterodimer partner (FXR-SHP) signalling and increased the expression of bile acid synthesis genes (P < 0.05). Our results explored the underlying mechanisms by which HLP accelerated cholesterol consumption to anti-hypercholesterolemia and anti-diabetic by inhibiting liver FXR-SHP signaling. HLP's effect on bile acid regulation provides insights into treating T2DM.PMID:37780338 | PMC:PMC10534105 | DOI:10.1016/j.fochx.2023.100741

Comparison of volatile and nonvolatile metabolites in green tea under hot-air drying and four heat-conduction drying patterns using widely targeted metabolomics

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jun 24;19:100767. doi: 10.1016/j.fochx.2023.100767. eCollection 2023 Oct 30.ABSTRACTHot-air and heat-conduction drying are the most common drying patterns in green tea production. However, the differences between them in terms of the resulting green tea chemical compounds have not been illustrated systematically. In this study, 515 volatile and 204 nonvolatile metabolites were selected to compare the differences between hot-air drying green tea (HAGT) and four heat-conduction drying green teas (HCDGTs) using widely targeted metabolomics. The results showed notable changes in volatile compounds; for example, two kinds of HCDGTs preferred to form chestnut-like and caramel-like key odorants. In addition, 14 flavonol glycosides, 10 catechins, 9 phenolic acids, 8 amino acids, 7 flavonols, and 3 sugars were significantly changed between HAGT and HCDGTs (p < 0.05), presenting a tremendous discrepancy in the transformation of nonvolatile compounds. Our results provide clear guidance for the precise manufacturing of green tea by four common heat-drying patterns and hot air-drying patterns.PMID:37780330 | PMC:PMC10534119 | DOI:10.1016/j.fochx.2023.100767

Variations in microbial diversity and chemical components of raw dark tea under different relative humidity storage conditions

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Sep 2;19:100863. doi: 10.1016/j.fochx.2023.100863. eCollection 2023 Oct 30.ABSTRACTRaw dark tea (RDT) usually needs to be stored for a long time to improve its quality under suitable relative humidity (RH). However, the impact of RH on tea quality is unclear. In this study, we investigated the metabolites and microbial diversity, and evaluated the sensory quality of RDT stored under three RH conditions (1%, 57%, and 88%). UHPLC-Q-TOF-MS analysis identified 144 metabolites, including catechins, flavonols, phenolic acids, amino acids, and organic acids. 57% RH led to higher levels of O-methylated catechin derivatives, polymerized catechins, and flavonols/flavones when compared to 1% and 88% RH. The best score in sensory evaluation was also obtained by 57% RH. Aspergillus, Gluconobacter, Kluyvera, and Pantoea were identified as the core functional microorganisms in RDT under different RH storage conditions. Overall, the findings provided new insights into the variation of microbial communities and chemical components under different RH storage conditions.PMID:37780317 | PMC:PMC10534245 | DOI:10.1016/j.fochx.2023.100863

Alfalfa leaf meal as a new protein feedstuff improves meat quality by modulating lipid metabolism and antioxidant capacity of finishing pigs

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jul 27;19:100815. doi: 10.1016/j.fochx.2023.100815. eCollection 2023 Oct 30.ABSTRACTThe effects of alfalfa leaf meal (ALM) on the meat quality of finishing pigs are largely unknown. Here, we investigated the effects of ALM diet on meat quality by replacing 0%, 25%, 50%, and 75% of soybean meal in the diet of finishing pigs, respectively. The findings showed that 25% ALM diet increased the IMF, cooked meat rate, a* and antioxidant capacity of longissimus dorsi (LD), improved amino acid composition, increased MUFA content, and increased LD lipid synthesis and mRNA expression of antioxidation-related genes. At the same time, ALM diet altered serum lipid metabolism (TG, FFA). Correlation analysis showed that antioxidant capacity was positively correlated with meat quality. In addition, metabolomic analysis of LD showed that the main metabolites of 25% ALM diet altered stachydrine and l-carnitine were associated with meat quality and antioxidant capacity. In conclusion, ALM replacing 25% soybean meal diet can improve the meat quality of pigs.PMID:37780297 | PMC:PMC10534147 | DOI:10.1016/j.fochx.2023.100815

Regulatory effect of lactulose on intestinal flora and serum metabolites in colitis mice: <em>In vitro</em> and <em>in vivo</em> evaluation

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Aug 11;19:100821. doi: 10.1016/j.fochx.2023.100821. eCollection 2023 Oct 30.ABSTRACTLactulose is a common component in foods. However, the effect of lactulose on intestinal flora and overall metabolic levels remains unclear. Therefore, this study aims to explore the regulative role of lactulose on intestinal flora and serum metabolites via in vitro simulated colonic fermentation model and in vivo colitis mouse model. The results showed that lactulose significantly enriched beneficial bacteria including Dubosiella and Bifidobacterium, and reduced pathogenic bacteria such as Fusobacterium. Moreover, lactulose significantly inhibited dextran sodium sulfate-induced body weight loss, colon shortening, colonic inflammatory infiltration, and pro-inflammatory cytokines IL-6, TNF-α, IL-17, and IL-1β. Lactulose significantly affected serum metabolome in colitis mice and total 24 metabolites representing a high inter-group difference were obtained. Correlation analysis revealed that the changes in serum metabolites were closely associated with the role of intestinal flora, and thus affected phenotypic indicators. Our study provides a reference for nutritional characteristics and application scenarios of dietary lactulose.PMID:37780294 | PMC:PMC10534180 | DOI:10.1016/j.fochx.2023.100821

Untargeted metabolomics and conventional quality characterization of rowanberry pomace ingredients in meatballs

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jun 28;19:100761. doi: 10.1016/j.fochx.2023.100761. eCollection 2023 Oct 30.ABSTRACTIn this study, a rowanberry pomace defatted with supercritical CO2 (2%-AC), its ethanolic extract (1%-E) and extraction residue (2%-R), were tested in meatball preparation. The meatballs with 1%-E demonstrated the highest in vitro radical scavenging capacity. In the case of 1%-E the pH of meatballs was significantly lower compared to the control sample (P = 0.0132) on the 5-day. The lowest cooking loss was achieved when the meatballs contained mainly fibre-rich 2%-R. The UHPLC method detected 184 metabolites, including strong antioxidants, such as chlorogenic acids, 3',4'-methylenedioxy-5,7-dimethylepicatechin, hyperin, isoquercitrin. The 1%-E was particularly effective against the development of unpleasant off-flavours caused by carbonyl compounds. Consistently, the decrease in lipid oxidation, indicated by reduced 7-dodecenal and 2,4-heptadienal contents, has been observed following the addition of rowanberry extract to meatballs. Metabolomics coupled with conventional quality evaluations provided a deeper understanding of the potential utilization and valorisation of different rowanberry pomace extracts as meat ingredients.PMID:37780283 | PMC:PMC10534112 | DOI:10.1016/j.fochx.2023.100761

A comprehensive review of the current trends and recent advancements on the authenticity of honey

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Aug 28;19:100850. doi: 10.1016/j.fochx.2023.100850. eCollection 2023 Oct 30.ABSTRACTThe authenticity of honey currently poses challenges to food quality control, thus requiring continuous modernization and improvement of related analytical methodologies. This review provides a comprehensively overview of honey authenticity challenges and related analytical methods. Firstly, direct and indirect methods of honey adulteration were described in detail, commenting the existing challenges in current detection methods and market supervision approaches. As an important part, the integrated metabolomic workflow involving sample processing procedures, instrumental analysis techniques, and chemometric tools in honey authenticity studies were discussed, with a focus on their advantages, disadvantages, and scopes. Among them, various improved microscale extraction methods, combined with hyphenated instrumental analysis techniques and chemometric data processing tools, have broad application potential in honey authenticity research. The future of honey authenticity determination will involve the use of simplified and portable methods, which will enable on-site rapid detection and transfer detection technologies from the laboratory to the industry.PMID:37780275 | PMC:PMC10534224 | DOI:10.1016/j.fochx.2023.100850

Analytical strategies based on untargeted and targeted metabolomics for the accurate authentication of organic milk from Jersey and Yak

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jul 8;19:100786. doi: 10.1016/j.fochx.2023.100786. eCollection 2023 Oct 30.ABSTRACTOrganic milk has a high risk of food fraud as it can easily be adulterated with non-organic milk. This study aimed to identify metabolite markers for assessing the authenticity of organic milk from Jersey and Yak. In the untargeted strategy, ultra-high performance liquid chromatography-Q Exactive HF-X mass spectrometer coupled with chemometrics analysis was used to screen and identify tentative markers of organic milk from Jersey and Yak. In the targeted strategy, a quick and easy method of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to quantify three markers. The peptide of Thr-Ala-Val and D-biotin were determined to be metabolite markers for distinguishing organic and non-organic Jersey milk, whereas trimethylamine N-oxide was determined to be a metabolite marker for distinguishing organic and non-organic Yak milk. These findings provide critical information to facilitate assessments of organic milk authenticity.PMID:37780248 | PMC:PMC10534096 | DOI:10.1016/j.fochx.2023.100786

Insight into the differences of meat quality between Qinghai white Tibetan sheep and black Tibetan sheep from the perspective of metabolomics and rumen microbiota

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Aug 16;19:100843. doi: 10.1016/j.fochx.2023.100843. eCollection 2023 Oct 30.ABSTRACTThe purpose of this study was to investigate the differences in meat quality between two local breeds of Tibetan sheep, the White Tibetan sheep and the Black Tibetan sheep in Qinghai, and to search for metabolic mechanisms that produce meat quality differences by analyzing differential metabolites and key rumen microorganisms. The meat quality results showed that one breed, SG73, was superior to the other (WG). Further investigation identified differences in the composition of muscle metabolites and rumen microorganisms between the two Tibetan sheep breeds. It also regulates muscle tenderness, water retention, fat content and the composition and content of AA and FA through two major metabolic pathways, AA metabolism and carbohydrate metabolism. These findings could be beneficial for the development of breeding strategies for Tibetan sheep in Qinghai in the future.PMID:37780244 | PMC:PMC10534161 | DOI:10.1016/j.fochx.2023.100843

Metabolomic comparison of meat quality and metabolites of geese breast muscle at different ages

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jun 27;19:100775. doi: 10.1016/j.fochx.2023.100775. eCollection 2023 Oct 30.ABSTRACTThe purpose of this study was to distinguish the effect of age on the meat quality and chemical composition of Yangzhou goose breast meat. Nontargeted metabolomics analysis (UHPLC-MS/MS) was used to distinguish the metabolic composition of goose meat at different ages, and Pearson's correlations between differential metabolites and key meat parameters were assessed. Compared with goslings, adult geese had lighter, redder and chewier meat (p < 0.05). Metabolite analysis revealed significant differences in nucleosides, organic acids, amino acids and sugars. Levels of IMP, xanthosine, pretyrosine and l-threonine were significantly higher in older meat (p < 0.05) and positively correlated with meat freshness indicators. However, pyruvic acid, l-cysteine and glucose 6-phosphate were up-regulated in gosling meat (p < 0.05), which were important flavor compounds. These results facilitate the further investigation of changes in goose meat composition and provide biomarkers for determining goose meat quality at different ages.PMID:37780242 | PMC:PMC10534087 | DOI:10.1016/j.fochx.2023.100775

Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach

Mon, 02/10/2023 - 12:00
Front Genet. 2023 Sep 14;14:1231682. doi: 10.3389/fgene.2023.1231682. eCollection 2023.ABSTRACTIntroduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood. Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach. Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy. Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies.PMID:37779912 | PMC:PMC10536237 | DOI:10.3389/fgene.2023.1231682

Metabolite profiles and DNA methylation in metabolic syndrome: a two-sample, bidirectional Mendelian randomization

Mon, 02/10/2023 - 12:00
Front Genet. 2023 Sep 15;14:1184661. doi: 10.3389/fgene.2023.1184661. eCollection 2023.ABSTRACTIntroduction: Metabolic syndrome (MetS) increases the risk of cardiovascular disease and death. Previous '-omics' studies have identified dysregulated serum metabolites and aberrant DNA methylation in the setting of MetS. However, the relationship between the metabolome and epigenome have not been elucidated. In this study, we identified serum metabolites associated with MetS and DNA methylation, and we conducted bidirectional Mendelian randomization (MR) to assess causal relationships between metabolites and methylation. Methods: We leveraged metabolomic and genomic data from a national United States cohort of older adults (REGARDS), as well as metabolomic, epigenomic, and genomic data from a family-based study of hypertension (HyperGEN). We conducted metabolite profiling for MetS in REGARDS using weighted logistic regression models and validated them in HyperGEN. Validated metabolites were selected for methylation studies which fit linear mixed models between metabolites and six CpG sites previously linked to MetS. Statistically significant metabolite-CpG pairs were selected for two-sample, bidirectional MR. Results: Forward MR indicated that glucose and serine metabolites were causal on CpG methylation near CPT1A [B(SE): -0.003 (0.002), p = 0.028 and B(SE): 0.029 (0.011), p = 0.030, respectively] and that serine metabolites were causal on ABCG1 [B(SE): -0.008(0.003), p = 0.006] and SREBF1 [B(SE): -0.009(0.004), p = 0.018] methylation, which suggested a protective effect of serine. Reverse MR showed a bidirectional relationship between cg06500161 (ABCG1) and serine [B(SE): -1.534 (0.668), p = 0.023]. Discussion: The metabolome may contribute to the relationship between MetS and epigenetic modifications.PMID:37779905 | PMC:PMC10540781 | DOI:10.3389/fgene.2023.1184661

Artificial Intelligence and Machine Learning in Pharmacological Research: Bridging the Gap Between Data and Drug Discovery

Mon, 02/10/2023 - 12:00
Cureus. 2023 Aug 30;15(8):e44359. doi: 10.7759/cureus.44359. eCollection 2023 Aug.ABSTRACTArtificial intelligence (AI) has transformed pharmacological research through machine learning, deep learning, and natural language processing. These advancements have greatly influenced drug discovery, development, and precision medicine. AI algorithms analyze vast biomedical data identifying potential drug targets, predicting efficacy, and optimizing lead compounds. AI has diverse applications in pharmacological research, including target identification, drug repurposing, virtual screening, de novo drug design, toxicity prediction, and personalized medicine. AI improves patient selection, trial design, and real-time data analysis in clinical trials, leading to enhanced safety and efficacy outcomes. Post-marketing surveillance utilizes AI-based systems to monitor adverse events, detect drug interactions, and support pharmacovigilance efforts. Machine learning models extract patterns from complex datasets, enabling accurate predictions and informed decision-making, thus accelerating drug discovery. Deep learning, specifically convolutional neural networks (CNN), excels in image analysis, aiding biomarker identification and optimizing drug formulation. Natural language processing facilitates the mining and analysis of scientific literature, unlocking valuable insights and information. However, the adoption of AI in pharmacological research raises ethical considerations. Ensuring data privacy and security, addressing algorithm bias and transparency, obtaining informed consent, and maintaining human oversight in decision-making are crucial ethical concerns. The responsible deployment of AI necessitates robust frameworks and regulations. The future of AI in pharmacological research is promising, with integration with emerging technologies like genomics, proteomics, and metabolomics offering the potential for personalized medicine and targeted therapies. Collaboration among academia, industry, and regulatory bodies is essential for the ethical implementation of AI in drug discovery and development. Continuous research and development in AI techniques and comprehensive training programs will empower scientists and healthcare professionals to fully exploit AI's potential, leading to improved patient outcomes and innovative pharmacological interventions.PMID:37779744 | PMC:PMC10539991 | DOI:10.7759/cureus.44359

Glutamate-pantothenate pathway promotes antibiotic resistance of <em>Edwardsiella tarda</em>

Mon, 02/10/2023 - 12:00
Front Microbiol. 2023 Sep 13;14:1264602. doi: 10.3389/fmicb.2023.1264602. eCollection 2023.ABSTRACTAlthough cellular metabolic states have been shown to modulate bacterial susceptibility to antibiotics, the interaction between glutamate (Glu) and chloramphenicol (CAP) resistance remains unclear because of the specificity of antibiotics and bacteria. We found that the level of Glu was upregulated in the CAP-resistant strain of Edwardsiella tarda according to a comparative metabolomics approach based on LC-MS/MS. Furthermore, we verified that exogenous metabolites related to Glu, the tricarboxylic acid (TCA) cycle, and glutathione (GSH) metabolism could promote CAP resistance in survival assays. If GSH metabolism or the TCA cycle is inhibited by L-buthionine sulfoximine or propanedioic acid, the promotion of CAP resistance by Glu in the corresponding pathway disappears. According to metabolomic analysis, exogenous Glu could change pantothenate metabolism, affecting GSH biosynthesis and the TCA cycle. These results showed that the glutamate-pantothenate pathway could promote CAP resistance by being involved in the synthesis of GSH, entering the TCA cycle by direct deamination, or indirectly affecting the metabolism of the two pathways by pantothenate. These results extend our knowledge of the effect of Glu on antibiotic resistance and suggest that the potential effect, which may aggravate antibiotic resistance, should be considered before Glu and GSH administration in the clinic.PMID:37779691 | PMC:PMC10533917 | DOI:10.3389/fmicb.2023.1264602

Exploring the potential mechanism of <em>Rubus corchorifolius</em> L. fruit polyphenol-rich extract in mitigating non-alcoholic fatty liver disease by integration of metabolomics and transcriptomics profiling

Mon, 02/10/2023 - 12:00
Food Funct. 2023 Oct 2. doi: 10.1039/d3fo02653a. Online ahead of print.ABSTRACTNonalcoholic fatty liver disease (NAFLD), as the commonest chronic liver disease, is accompanied by liver oxidative stress and inflammatory responses. Herein, the extract obtained from Rubus corchorifolius fruits was purified and characterized for its polyphenol composition. The liver protective effect of the purified R. corchorifolius fruit extract (RCE) on mice with high-fat-diet (HFD)-induced NAFLD were investigated, and the potential mechanisms were explored through the integration of transcriptomics and metabolomics. Results showed that the polyphenolic compounds in RCE mainly included (-)-epigallocatechin, procyanidin B2, keracyanin, vanillin, dihydromyricetin, and ellagic acid. In addition, RCE intervention ameliorated liver and mitochondrial damage, which was evidenced by decreased indices of oxidative stress, liver function markers, and lipid profile levels. The liver metabonomics research revealed that RCE intervention affected the metabolic pathways of metabolites, including linoleic acid metabolism, galactose metabolism, alanine, aspartate and glutamate metabolism, retinol metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, aminoacyl-tRNA biosynthesis, riboflavin metabolism, starch and sucrose metabolism, and arachidonic acid metabolism. Additionally, liver transcriptomics research indicated that pathways like fatty acid degradation, circadian rhythm, valine, leucine and isoleucine degradation, primary bile acid biosynthesis, cytokine-cytokine receptor interaction, adipocytokine signaling pathway, glutathione metabolism, lipid and atherosclerosis were significantly enriched. The transcriptomics and metabolomics analysis demonstrated that RCE intervention had significant modulatory effects on the metabolic pathways associated with glycolipid metabolism. Moreover, RT-PCR results verified that RCE intervention regulated liver mRNA levels associated with the inflammatory response. Therefore, our findings suggest that the intake of RCE might be an effective strategy to alleviate liver damage.PMID:37779461 | DOI:10.1039/d3fo02653a

Metabolite profiling and antioxidant capacity of natural Ophiocordyceps gracilis and its cultures using LC-MS/MS-based metabolomics: Comparison with Ophiocordyceps sinensis

Mon, 02/10/2023 - 12:00
Phytochem Anal. 2023 Oct 1. doi: 10.1002/pca.3289. Online ahead of print.ABSTRACTINTRODUCTION: Ophiocordyceps gracilis is an entomopathogenic fungus and a precious traditional Chinese medicine with similar medicinal properties to Ophiocordyceps sinensis. However, information on the metabolite profiles of natural O. gracilis and its cultures is lacking, which limits their utilization.OBJECTIVE: The metabolic variations and antioxidant activities of O. gracilis cultures and natural O. gracilis were analyzed to evaluate the nutritional and medicinal value of O. gracilis and its cultures.METHOD: The metabolite profiles of O. gracilis cultures (fruiting bodies and aerial mycelia), natural O. gracilis, and natural O. sinensis were compared by LC-MS/MS coupled with multivariate data analysis. Furthermore, their antioxidant activities were evaluated based on their DPPH• , ABTS•+ , and • OH scavenging abilities.RESULTS: A total of 612 metabolites were identified, and the metabolic compositions of the four Cordyceps samples were similar, with differences observed in the levels of some metabolites. There were 126 differential metabolites between natural O. gracilis and natural O. sinensis, among which fatty acids, carbohydrates, and secondary metabolites are predominant in natural O. gracilis. Furthermore, 116 differential metabolites between O. gracilis cultures and natural Cordyceps were identified, with generally higher levels in O. gracilis cultures than in natural Cordyceps. O. gracilis cultivated fruiting bodies exhibited the strongest antioxidant capacity among Cordyceps samples. Additionally, 46 primary and 24 secondary differential metabolites contribute to antioxidant activities.CONCLUSION: This study provides a reference for the application of natural O. gracilis and its cultures in functional food and medicine from the perspective of metabolites and antioxidant capacity.PMID:37779226 | DOI:10.1002/pca.3289

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