PubMed
Golden 2-like Transcription Factors Regulate Photosynthesis under UV-B Stress by Regulating the Calvin Cycle
Plants (Basel). 2024 Jul 5;13(13):1856. doi: 10.3390/plants13131856.ABSTRACTUV-B stress can affect plant growth at different levels, and although there is a multitude of evidence confirming the effects of UV-B radiation on plant photosynthesis, there are fewer studies using physiological assays in combination with multi-omics to investigate photosynthesis in alpine plants under stressful environments. Golden 2-like (G2-like/GLK) transcription factors (TFs) are highly conserved during evolution and may be associated with abiotic stress. In this paper, we used Handy-PEA and Imaging-PAM Maxi to detect chlorophyll fluorescence in leaves of Rhododendron chrysanthum Pall. (R. chrysanthum) after UV-B stress, and we also investigated the effect of abscisic acid (ABA) on photosynthesis in plants under stress environments. We used a combination of proteomics, widely targeted metabolomics, and transcriptomics to study the changes of photosynthesis-related substances after UV-B stress. The results showed that UV-B stress was able to impair the donor side of photosystem II (PSII), inhibit electron transfer and weaken photosynthesis, and abscisic acid was able to alleviate the damage caused by UV-B stress to the photosynthetic apparatus. Significant changes in G2-like transcription factors occurred in R. chrysanthum after UV-B stress, and differentially expressed genes localized in the Calvin cycle were strongly correlated with members of the G2-like TF family. Multi-omics assays and physiological measurements together revealed that G2-like TFs can influence photosynthesis in R. chrysanthum under UV-B stress by regulating the Calvin cycle. This paper provides insights into the study of photosynthesis in plants under stress, and is conducive to the adoption of measures to improve photosynthesis in plants under stress to increase yield.PMID:38999696 | DOI:10.3390/plants13131856
First Data on the (Poly)phenolic Profiling of Farmacista Honorati Persimmon Fruit (<em>Diospyros kaki</em> Thunb.) at Commercial Harvest and after Treatments for Astringency Removal
Plants (Basel). 2024 Jun 26;13(13):1768. doi: 10.3390/plants13131768.ABSTRACTThis study aims to provide the first report on the soluble and polyphenolic profiles of "Farmacista Honorati" (FH) persimmons, which is a marketed cultivar with no existing data on its nutraceutical value. Total soluble tannins (TSTs) and major soluble (poly)phenols in FH fruits before and after post-harvest commercial treatments with carbon dioxide and ethylene were analyzed. Fruits at commercial harvest had a TST content of 1022 ± 286 mg GAL/100 g d.w. Whereas, after deastringency treatments, an 85% and 83% reduction were observed for carbon dioxide- and ethylene-treated fruits, respectively. Carbon dioxide treatment resulted in the insolubilization of tannins around comparable values in most fruit cultivars, despite the variable soluble tannin content in untreated fruit. By targeted metabolomic profiling, nineteen (poly)phenolic substances were quantified in the investigated untreated and treated fruits. Gallic acid (99 mg/100 g d.w.), (+)-catechin (1.8 mg/100 g d.w.), ellagic acid (1.2 mg/100 g d.w.), and (-)-epicatechin (1.1 mg/100 g d.w.) were the predominant compounds in the untreated FH samples. After the application of post-harvest treatments, a non-nutraceutical relevant decrease of 8-19% in the targeted (poly)phenolic content was generally observed. Ethylene induced the most significant reduction in the individual (poly)phenolic compounds in the FH fruits.PMID:38999608 | DOI:10.3390/plants13131768
UV-B Radiation Enhances <em>Epimedium brevicornu</em> Maxim. Quality by Improving the Leaf Structure and Increasing the Icaritin Content
Plants (Basel). 2024 Jun 21;13(13):1720. doi: 10.3390/plants13131720.ABSTRACTEpimedium brevicornu Maxim. is a herbal plant with various therapeutic effects, and its aboveground tissues contain flavonol compounds such as icaritin that can be used to produce new drugs for the treatment of advanced liver cancer. Previous studies have shown that ultraviolet-B (UV-B, 280-315 nm) stress can increase the levels of flavonoid substances in plants. In the current study, we observed the microstructure of E. brevicornu leaves after 0, 5, 10, 15, and 20 d of UV-B radiation (60 μw·cm-2) and quality formation mechanism of E. brevicornu leaves after 0, 10, and 20 d of UV-B radiation by LC‒ESI‒MS/MS. The contents of flavonols such as icariside I, wushanicaritin, icaritin, and kumatakenin were significantly upregulated after 10 d of radiation. The results indicated that UV-B radiation for 10 d inhibited the morphological development of E. brevicornu but increased the content of active medicinal components, providing a positive strategy for epimedium quality improvement.PMID:38999560 | DOI:10.3390/plants13131720
Molecular Perspectives in Radioactive Iodine Theranostics: Current Redifferentiation Protocols for Mis-Differentiated Thyroid Cancer
J Clin Med. 2024 Jun 21;13(13):3645. doi: 10.3390/jcm13133645.ABSTRACTThyroid cancer molecular oncogenesis involves functional dedifferentiation. The initiating genomic alterations primarily affect the MAPK pathway signal transduction and generate an enhanced ERK output, which in turn results in suppression of the expression of transcription of the molecules of iodine metabolomics. The clinical end result of these molecular alterations is an attenuation in theranostic power of radioactive iodine (RAI). The utilization of RAI in systemic therapy of metastatic disease requires restoration of the functional differentiation. This concept has been accomplished by modulation of MAPK signaling. Objective responses have been demonstrated in metastatic disease settings. RAI-refractoriness in "differentiated thyroid cancers" remains a clinical problem despite optimized RAI administration protocols. Functional mis-differentiation and associated RAI-indifference are the underlying primary obstacles. MAPK pathway modulation offers a potential for reversal of RAI-indifference and combat refractoriness. This review presents the latest clinical experience and protocols for the redifferentiation of radioiodine-refractory mis-differentiated thyroid cancer, providing a comprehensive overview of the current protocols and intervention strategies used by leading institutions. Timing and techniques of imaging, thyrotropin (TSH) stimulation methods, and redifferentiation agents are presented. The efficacy and limitations of various approaches are discussed, providing an overview of the advantages and disadvantages associated with each of the protocols.PMID:38999211 | DOI:10.3390/jcm13133645
Widely Targeted Metabolomic Analysis Reveals the Improvement in Panax notoginseng Triterpenoids Triggered by Arbuscular Mycorrhizal Fungi via UPLC-ESI-MS/MS
Molecules. 2024 Jul 8;29(13):3235. doi: 10.3390/molecules29133235.ABSTRACTPanax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants.PMID:38999186 | DOI:10.3390/molecules29133235
Elucidating the Phytochemical Landscape of Leaves, Stems, and Tubers of Codonopsis convolvulacea through Integrated Metabolomics
Molecules. 2024 Jul 4;29(13):3193. doi: 10.3390/molecules29133193.ABSTRACTCodonopsis convolvulacea is a highly valued Chinese medicinal plant containing diverse bioactive compounds. While roots/tubers have been the main medicinal parts used in practice, leaves and stems may also harbor valuable phytochemicals. However, research comparing volatiles across tissues is lacking. This study performed metabolomic profiling of leaves, stems, and tubers of C. convolvulacea to elucidate tissue-specific accumulation patterns of volatile metabolites. Ultra-high performance liquid chromatography-tandem mass spectrometry identified 302 compounds, belonging to 14 classes. Multivariate analysis clearly differentiated the metabolic profiles of the three tissues. Numerous differentially accumulated metabolites (DAMs) were detected, especially terpenoids and esters. The leaves contained more terpenoids, ester, and alcohol. The stems accumulated higher levels of terpenoids, heterocyclics, and alkaloids with pharmaceutical potential. The tubers were enriched with carbohydrates like sugars and starch, befitting their storage role, but still retained reasonable amounts of valuable volatiles. The characterization of tissue-specific metabolic signatures provides a foundation for the selective utilization of C. convolvulacea parts. Key metabolites identified include niacinamide, p-cymene, tridecanal, benzeneacetic acid, benzene, and carveol. Leaves, stems, and tubers could be targeted for antioxidants, drug development, and tonics/nutraceuticals, respectively. The metabolomic insights can also guide breeding strategies to enhance the bioactive compound content in specific tissues. This study demonstrates the value of tissue-specific metabolite profiling for informing the phytochemical exploitation and genetic improvement of medicinal plants.PMID:38999145 | DOI:10.3390/molecules29133193
Study on <em>Oleum cinnamomi</em> Inhibiting <em>Cutibacterium acnes</em> and Its Covalent Inhibition Mechanism
Molecules. 2024 Jul 3;29(13):3165. doi: 10.3390/molecules29133165.ABSTRACTOleum cinnamomi (OCM) is a volatile component of the Cinnamomum cassia Presl in the Lauraceae family, which displays broad-spectrum antibacterial properties. It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 µg/mL and 180 µg/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.PMID:38999117 | DOI:10.3390/molecules29133165
A Support Vector Machine-Assisted Metabolomics Approach for Non-Targeted Screening of Multi-Class Pesticides and Veterinary Drugs in Maize
Molecules. 2024 Jun 26;29(13):3026. doi: 10.3390/molecules29133026.ABSTRACTThe contamination risks of plant-derived foods due to the co-existence of pesticides and veterinary drugs (P&VDs) have not been fully understood. With an increasing number of unexpected P&VDs illegally added to foods, it is essential to develop a non-targeted screening method for P&VDs for their comprehensive risk assessment. In this study, a modified support vector machine (SVM)-assisted metabolomics approach by screening eligible variables to represent marker compounds of 124 multi-class P&VDs in maize was developed based on the results of high-performance liquid chromatography-tandem mass spectrometry. Principal component analysis and orthogonal partial least squares discriminant analysis indicate the existence of variables with obvious inter-group differences, which were further investigated by S-plot plots, permutation tests, and variable importance in projection to obtain eligible variables. Meanwhile, SVM recursive feature elimination under the radial basis function was employed to obtain the weight-squared values of all the variables ranging from large to small for the screening of eligible variables as well. Pairwise t-tests and fold changes of concentration were further employed to confirm these eligible variables to represent marker compounds. The results indicate that 120 out of 124 P&VDs can be identified by the SVM-assisted metabolomics method, while only 109 P&VDs can be found by the metabolomics method alone, implying that SVM can promote the screening accuracy of the metabolomics method. In addition, the method's practicability was validated by the real contaminated maize samples, which provide a bright application prospect in non-targeted screening of contaminants. The limits of detection for 120 P&VDs in maize samples were calculated to be 0.3~1.5 µg/kg.PMID:38998975 | DOI:10.3390/molecules29133026
Uncovering Metabolic Alterations in HCT-116 Colon Cancer Cells upon Exposure to Bamboo Leaf Extract Obtained from <em>Guadua incana</em> Londoño
Molecules. 2024 Jun 23;29(13):2985. doi: 10.3390/molecules29132985.ABSTRACTMetabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.PMID:38998936 | DOI:10.3390/molecules29132985
Fermented <em>Gastrodia elata</em> Bl. Alleviates Cognitive Deficits by Regulating Neurotransmitters and Gut Microbiota in D-Gal/AlCl<sub>3</sub>-Induced Alzheimer's Disease-like Mice
Foods. 2024 Jul 8;13(13):2154. doi: 10.3390/foods13132154.ABSTRACTAlzheimer's disease (AD) is a common neurological disease with recognition ability loss symptoms and a major contributor to dementia cases worldwide. Gastrodia elata Bl. (GE), a food of medicine-food homology, has been reported to have a mitigating effect on memory and learning ability decline. However, the effect of GE fermented by Lactobacillus plantarum, Acetobacter pasteurianus, and Saccharomyces (FGE) on alleviating cognitive deficits in AD was not studied. Mice were randomly divided into six groups, control, model, donepezil, low, medium, and high doses of FGE, and D-Galactose/Aluminum chloride (D-Gal/AlCl3) was used to establish an AD-like mouse model. The results indicated that FGE could improve the production of neurotransmitters and relieve oxidative stress damage in AD-like mice, which was evidenced by the declined levels of amyloid-β (Aβ), Tau, P-Tau, acetylcholinesterase (AchE), and malondialdehyde (MDA), and increased acetylcholine (Ach), choline acetyltransferase (ChAT), and superoxide dismutase (SOD) levels in brain tissue. Notably, FGE could enhance the richness of the gut microbiota, especially for beneficial bacteria such as Lachnospira and Lactobacillus. Non-target metabolomics results indicated that FGE could affect neurotransmitter levels by regulating amino acid metabolic pathways to improve AD symptoms. The FGE possessed an ameliorative effect on AD by regulating neurotransmitters, oxidative stress levels, and gut microbiota and could be considered a good candidate for ameliorating AD.PMID:38998659 | DOI:10.3390/foods13132154
Sulfated Polysaccharides from Sea Cucumber Cooking Liquid Prevents Obesity by Modulating Gut Microbiome, Transcriptome, and Metabolite Profiles in Mice Fed a High-Fat Diet
Foods. 2024 Jun 26;13(13):2017. doi: 10.3390/foods13132017.ABSTRACTWe aimed to explore the anti-obesity mechanism from the microbiome, metabolome, and transcriptome viewpoints, focusing on the sulfated polysaccharides found in the cooking liquid of Apostichopus japonicus (CLSPAJ) to explore the potential mediators of the anti-obesity effects in mice fed a high-fat diet (HFD). The mice treated with CLSPAJ showed a decrease in obesity and blood lipid levels. Gut microbiome dysbiosis caused by the HFD was reversed after CLSPAJ supplementation, along with increased levels of indole-3-ethanol, N-2-succinyl-L-glutamic acid 5-semialdehyde, and urocanic acid. These increases were positively related to the increased Akkermansia, Lactobacillus, Roseburia, and Phascolarctobacterium. Transcriptome analysis showed that B cell receptor signaling and cytochrome P450 xenobiotic metabolism were the main contributors to the improvement in obesity. Metabolome-transcriptome analysis revealed that CLSPAJ reversal of obesity was mainly due to amino acid metabolism. These findings suggest that CLSPAJ could be a valuable prebiotic preparation for preventing obesity-related diseases.PMID:38998524 | DOI:10.3390/foods13132017
Harnessing Bacillus amyloliquefaciens for Amazake Production: Comparison with Aspergillus oryzae Amazake for Metabolomic Characteristics, Microbial Diversity, and Sensory Profile
Foods. 2024 Jun 26;13(13):2012. doi: 10.3390/foods13132012.ABSTRACTAmazake is a traditional, sweet, non-alcoholic Japanese beverage typically produced through koji fermentation by the fungus Aspergillus oryzae. However, alternative microorganisms such as Bacillus amyloliquefaciens offer potential advantages and novel possibilities for producing similar fermented beverages. This study aimed to replicate the ancestral beverage of amazake by replacing A. oryzae (W-20) with B. amyloliquefaciens (NCIMB 12077) and comparing their fermentation processes and resulting products. Our results show that the production of amazake with B. amyloliquefaciens (ABA) is not only possible but also results in a beverage that is otherwise distinct from traditional amazake (AAO). Saccharification was achievable in ABA at higher temperatures than in AAO, albeit with lower reducing sugar and enzymatic activity values. Amino acids and organic acids were more abundant in AAO, with cysteine being uniquely present in AAO and shikimic acid only being present in ABA. The volatile aroma compound profiles differed between the two beverages, with AAO exhibiting a greater abundance of aldehydes, and ABA a greater abundance of ketones and alcohols. Interestingly, despite these compositional differences, the two beverages showed similar consumer panel acceptance rates. An analysis of their microbial communities revealed pronounced differences between the amazakes, as well as temporal changes in ABA but not in AAO. This study provides promising insights into harnessing the potential of B. amyloliquefaciens as the primary microorganism in the fermentation process of amazake-like beverages, marking an important advancement in the field of fermented low-alcohol beverage production, with possible applications in other fermented foods.PMID:38998518 | DOI:10.3390/foods13132012
Widely Targeted Metabolomics Provides New Insights into Nutritional Profiling and Reveals the Flavonoid Pathway of Pea (Pisum sativum L.)
Foods. 2024 Jun 21;13(13):1970. doi: 10.3390/foods13131970.ABSTRACTTo learn more about the nutritional composition and health benefits for human consumers of peas, we used a widely targeted metabolomics-based approach to reveal the metabolite components from three main varieties, and a total of 1095 metabolites were identified. A comparison of 487 differentially accumulated metabolites shared among three varieties of fresh and dried peas found most of the amino acids and derivatives were downregulated and most of the lipids and flavonoids were upregulated in dried peas. Furthermore, comparing the main nutrient profiles exclusively showed that there were few differences in free fatty acids, sugars, vitamins, and alkaloids between dried and fresh peas. Peas are especially enriched with B-group vitamins. Through detailed identification and classification, the flavonoid pathway of peas was revealed; a variety of glycosylated derivatives from kaempferol, quercetin, and luteolin were confirmed to be abundant in peas. It was also found that isoflavones are richer in peas than in many other plants, and putatively the isoflavone synthesis pathway originates from liquiritigenin and naringenin. Our study not only offers guidance for understanding the nutritional components of peas, but also provides the basis for healthy diet analysis of the edible value and health benefits of peas.PMID:38998476 | DOI:10.3390/foods13131970
Comparative (1)H NMR-Based Metabolomics of Traditional Landrace and Disease-Resistant Chili Peppers (Capsicum annuum L.)
Foods. 2024 Jun 21;13(13):1966. doi: 10.3390/foods13131966.ABSTRACTChili peppers (Capsicum annuum L.) are economically valuable crops belonging to the Solanaceae family and are popular worldwide because of their unique spiciness and flavor. In this study, differences in the metabolomes of landrace (Subicho) and disease-resistant pepper cultivars (Bulkala and Kaltanbaksa) widely grown in Korea are investigated using a 1H NMR-based metabolomics approach. Specific metabolites were abundant in the pericarp (GABA, fructose, and glutamine) and placenta (glucose, asparagine, arginine, and capsaicin), highlighting the distinct physiological and functional roles of these components. Both the pericarp and placenta of disease-resistant pepper cultivars contained higher levels of sucrose and hexoses and lower levels of alanine, proline, and threonine than the traditional landrace cultivar. These metabolic differences are linked to enhanced stress tolerance and the activation of defense pathways, imbuing these cultivars with improved resistance characteristics. The present study provides fundamental insights into the metabolic basis of disease resistance in chili peppers, emphasizing the importance of multi-resistant varieties to ensure sustainable agriculture and food security. These resistant varieties ensure a stable supply of high-quality peppers, contributing to safer and more sustainable food production systems.PMID:38998472 | DOI:10.3390/foods13131966
Untargeted Metabolomic Analysis Reveals Plasma Differences between Mares with Endometritis and Healthy Ones
Animals (Basel). 2024 Jun 29;14(13):1933. doi: 10.3390/ani14131933.ABSTRACTThe aim of this study was to explore alterations in plasma metabolites among mares afflicted with endometritis. Mares were divided into two groups, namely, the equine endometritis group (n = 8) and the healthy control group (n = 8), which included four pregnant and four non-pregnant mares, using a combination of clinical assessment and laboratory confirmation. Plasma samples from both groups of mares were analyzed through untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics. A total of 28 differentially abundant metabolites were identified by screening and identifying differentially abundant metabolites and analyzing the pathway enrichment of differentially. Ten metabolites were identified as potential biomarkers for the diagnosis of endometritis in mares. Among them, seven exhibited a decrease in the endometritis groups, including hexadecanedioic acid, oleoyl ethanolamide (OEA), [fahydroxy(18:0)]12_13-dihydroxy-9z-octa (12,13-diHOME), deoxycholic acid 3-glucuronide (DCA-3G), 2-oxindole, and (+/-)9-HPODE, and 13(S)-HOTRE. On the other hand, three metabolites, adenosine 5'-monophosphate (AMP), 5-hydroxy-dl-tryptophan (5-HTP), and l-formylkynurenine, demonstrated an increase. These substances primarily participate in the metabolism of tryptophan and linolenic acid, as well as fat and energy. In conclusion, metabolomics revealed differentially abundant metabolite changes in patients with mare endometritis. These specific metabolites can be used as potential biomarkers for the non-invasive diagnosis of mare endometritis.PMID:38998045 | DOI:10.3390/ani14131933
Metabolic Response to Small Molecule Therapy in Colorectal Cancer Tracked with Raman Spectroscopy and Metabolomics
Angew Chem Int Ed Engl. 2024 Jul 12:e202410919. doi: 10.1002/anie.202410919. Online ahead of print.ABSTRACTDespite numerous screening tools for colorectal cancer (CRC), 25% of patients are diagnosed with advanced disease. Novel diagnostic technologies that are early, accurate, and rapid are imperative to assess the therapeutic efficacy of clinical drugs and identify new biomarkers of treatment response. Here Raman spectroscopy (RS) was used to track metabolic reprogramming in KRAS-mutant HCT116 and SW837 cells, and KRAS wild-type CC cells. RS combined with multivariate analysis methods distinguished nonresponsive, partially responsive, and responsive cells treated with cetuximab, a monoclonal antibody for EGFR inhibition, sotorasib, a clinically approved KRAS inhibitor, and various doses of trametinib, an inhibitor of the MAPK pathway. Cells treated with a combination of subtoxic doses of trametinib and BKM120, an inhibitor of the PI3K pathway, showed a synergistic response between the two pathways. Using a supervised machine learning regression model, we established a scoring methodology trained to a priori predict therapeutic response to new treatment combinations. RS metabolites were verified with mass spectrometry, and enrichment pathways were identified, including amino acid, purine, and nicotinate and nicotinamide metabolism that differentiated monotherapy from combination therapy. Our approach may ultimately be applicable to patient-derived primary cells and cultures of patient tumors to predict effective drugs for individualized care.PMID:38995663 | DOI:10.1002/anie.202410919
PhosphoLipidome Alteration Induced by <em>Clostridioides difficile</em> Toxin B in Enteric Glial Cells
Cells. 2024 Jun 26;13(13):1103. doi: 10.3390/cells13131103.ABSTRACTClostridioides difficile (C. difficile) is responsible for a spectrum of nosocomial/antibiotic-associated gastrointestinal diseases that are increasing in global incidence and mortality rates. The C. difficile pathogenesis is due to toxin A and B (TcdA/TcdB), both causing cytopathic and cytotoxic effects and inflammation. Recently, we demonstrated that TcdB induces cytopathic and cytotoxic (apoptosis and necrosis) effects in enteric glial cells (EGCs) in a dose/time-dependent manner and described the underlying signaling. Despite the role played by lipids in host processes activated by pathogens, to counter infection and/or induce cell death, to date no studies have investigated lipid changes induced by TcdB/TcdA. Here, we evaluated the modification of lipid composition in our in vitro model of TcdB infection. Apoptosis, cell cycle, cell viability, and lipidomic profiles were evaluated in EGCs treated for 24 h with two concentrations of TcdB (0.1 ng/mL; 10 ng/mL). In EGCs treated with the highest concentration of TcdB, not only an increased content of total lipids was observed, but also lipidome changes, allowing the separation of TcdB-treated cells and controls into different clusters. The statistical analyses also allowed us to ascertain which lipid classes and lipid molecular species determine the clusterization. Changes in lipid species containing inositol as polar head and plasmalogen phosphatidylethanolamine emerged as key indicators of altered lipid metabolism in TcdB-treated EGCs. These results not only provide a picture of the phospholipid profile changes but also give information regarding the lipid metabolism pathways altered by TcdB, and this might represent an important step for developing strategies against C. difficile infection.PMID:38994956 | DOI:10.3390/cells13131103
Regulatory Peptide Encoded by the Primary Transcript of miR396a Influences Gene Expression and Root Development in <em>Solanum lycopersicum</em>
J Agric Food Chem. 2024 Jul 12. doi: 10.1021/acs.jafc.4c03588. Online ahead of print.ABSTRACTMicroRNAs (miRNAs) are the processing products of primary miRNAs (pri-miRNAs) that regulate the expression of target genes. Recent studies have demonstrated that some pri-miRNAs can encode small peptides (miPEPs) that perform significant biological functions. The function of miPEPs in tomatoes, an important model horticultural crop, remains to be investigated. Here, we characterized the primary sequence of tomato miR396a using 5' RACE and confirmed the presence of miPEP396a in tomato by verifying the translational activity of the start codon. It primarily resides in the nucleus to exert its function and additionally regulates the expression of pri-miR396a, miR396a, and its target genes. Transcriptomic and metabolomic analyses showed that in vitro synthesis of miPEP396a significantly increased the expression of genes related to phenylpropanoid biosynthesis and hormones in tomato. Meanwhile, our in vitro application of miPEP396a in tomato significantly inhibited the elongation of tomato primary roots. In conclusion, our results indicate that miPEP396a regulates root growth in tomato by specifically promoting miR396a expression, provide insight into the function of miPEPs in tomato and potential applications.PMID:38994823 | DOI:10.1021/acs.jafc.4c03588
A cross-omics data analysis strategy for metabolite-microbe pair identification
Proteomics. 2024 Jul 12:e2400035. doi: 10.1002/pmic.202400035. Online ahead of print.ABSTRACTGiven the pivotal roles of metabolomics and microbiomics, numerous data mining approaches aim to uncover their intricate connections. However, the complex many-to-many associations between metabolome-microbiome profiles yield numerous statistically significant but biologically unvalidated candidates. To address these challenges, we introduce BiOFI, a strategic framework for identifying metabolome-microbiome correlation pairs (Bi-Omics). BiOFI employs a comprehensive scoring system, incorporating intergroup differences, effects on feature correlation networks, and organism abundance. Meanwhile, it establishes a built-in database of metabolite-microbe-KEGG functional pathway linking relationships. Furthermore, BiOFI can rank related feature pairs by combining importance scores and correlation strength. Validation on a dataset of cesarean-section infants confirms the strategy's validity and interpretability. The BiOFI R package is freely accessible at https://github.com/chentianlu/BiOFI.PMID:38994817 | DOI:10.1002/pmic.202400035
Updating and profiling the natural product-likeness of Latin American compound libraries
Mol Inform. 2024 Jul;43(7):e202400052. doi: 10.1002/minf.202400052. Epub 2024 Jun 21.ABSTRACTCompound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.PMID:38994633 | DOI:10.1002/minf.202400052