PubMed

Molecules. 2024 Mar 27;29(7):1485. doi: 10.3390/molecules29071485.ABSTRACTThe color of the pericarp is a crucial characteristic that influences the marketability of papaya fruit. Prior to ripening, normal papaya exhibits a green pericarp, whereas the cultivar 'Zihui' displays purple ring spots on the fruit tip, which significantly affects the fruit's visual appeal. To understand the mechanism behind the formation of purple pericarp, this study performed a thorough examination of the transcriptome, plant hormone, and metabolome. Based on the UPLC-ESI-MS/MS system, a total of 35 anthocyanins and 11 plant hormones were identified, with 27 anthocyanins and two plant hormones exhibiting higher levels of abundance in the purple pericarp. In the purple pericarp, 14 anthocyanin synthesis genes were up-regulated, including CHS, CHI, F3H, F3'5'H, F3'H, ANS, OMT, and CYP73A. Additionally, through co-expression network analysis, three MYBs were identified as potential key regulators of anthocyanin synthesis by controlling genes encoding anthocyanin biosynthesis. As a result, we have identified numerous key genes involved in anthocyanin synthesis and developed new insights into how the purple pericarp of papaya is formed.PMID:38611765 | DOI:10.3390/molecules29071485

Molecules. 2024 Mar 26;29(7):1473. doi: 10.3390/molecules29071473.ABSTRACTThe fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, α-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better α-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.PMID:38611753 | DOI:10.3390/molecules29071473

Diagnostics (Basel). 2024 Mar 24;14(7):682. doi: 10.3390/diagnostics14070682.ABSTRACTINTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy. Despite high cure rates, several questions remain regarding predisposition, response to treatment, and prognosis of the disease. The role of intermediary metabolism in the individualized mechanistic pathways of the disease is unclear. We have hypothesized that children with any (sub)type of ALL have a distinct metabolomic fingerprint at diagnosis when compared: (i) to a control group; (ii) to children with a different (sub)type of ALL; (iii) to the end of the induction treatment.MATERIALS AND METHODS: In this prospective case-control study (NCT03035344), plasma and urinary metabolites were analyzed in 34 children with ALL before the beginning (D0) and at the end of the induction treatment (D33). Their metabolic fingerprint was defined by targeted analysis of 106 metabolites and compared to that of an equal number of matched controls. Multivariate and univariate statistical analyses were performed using SIMCAP and scripts under the R programming language.RESULTS: Metabolomic analysis showed distinct changes in patients with ALL compared to controls on both D0 and D33. The metabolomic fingerprint within the patient group differed significantly between common B-ALL and pre-B ALL and between D0 and D33, reflecting the effect of treatment. We have further identified the major components of this metabolic dysregulation, indicating shifts in fatty acid synthesis, transfer and oxidation, in amino acid and glycerophospholipid metabolism, and in the glutaminolysis/TCA cycle.CONCLUSIONS: The disease type and time point-specific metabolic alterations observed in pediatric ALL are of particular interest as they may offer potential for the discovery of new prognostic biomarkers and therapeutic targets.PMID:38611595 | DOI:10.3390/diagnostics14070682

Plants (Basel). 2024 Apr 8;13(7):1041. doi: 10.3390/plants13071041.ABSTRACTGinseng (Panax ginseng C. A. Meyer) is a perennial plant with a long dormancy period. While some researchers employ gibberellin and other substances to stimulate premature germination, this method is limited to laboratory settings and cannot be applied to the field cultivation of ginseng. The mechanism underlying the germination of ginseng overwintering buds remains largely unexplored. Understanding the internal changes during the dormancy release process in the overwintering buds would facilitate the discovery of potential genes, metabolites, or regulatory pathways associated with it. In this study, we approximately determined the onset of dormancy release through morphological observations and investigated the process of dormancy release in ginseng overwintering buds using transcriptomic and metabolomic approaches. Our analyses revealed that the germination process of ginseng overwintering buds is regulated by multiple plant hormones, each acting at different times. Among these, abscisic acid (ABA) and gibberellic acid (GA) serve as classical signaling molecules regulating the dormancy process, while other hormones may promote the subsequent growth of overwintering buds. Additionally, metabolic pathways associated with arginine may be involved in the dormancy release process. Polyamines synthesized downstream may promote the growth of overwintering buds after dormancy release and participate in subsequent reproductive growth. This study provides insights into the germination process of ginseng overwintering buds at the molecular level and serves as a reference for further exploration of the detailed mechanism underlying ginseng overwintering germination in the future.PMID:38611569 | DOI:10.3390/plants13071041

Plants (Basel). 2024 Apr 3;13(7):1024. doi: 10.3390/plants13071024.ABSTRACTThe Australian Wet Tropics World Heritage Area (WTWHA) in northeast Queensland is home to approximately 18 percent of the nation's total vascular plant species. Over the past century, human activity and industrial development have caused global climate changes, posing a severe and irreversible danger to the entire land-based ecosystem, and the WTWHA is no exception. The current average annual temperature of WTWHA in northeast Queensland is 24 °C. However, in the coming years (by 2030), the average annual temperature increase is estimated to be between 0.5 and 1.4 °C compared to the climate observed between 1986 and 2005. Looking further ahead to 2070, the anticipated temperature rise is projected to be between 1.0 and 3.2 °C, with the exact range depending on future emissions. We identified 84 plant species, endemic to tropical montane cloud forests (TMCF) within the WTWHA, which are already experiencing climate change threats. Some of these plants are used in herbal medicines. This study comprehensively reviewed the metabolomics studies conducted on these 84 plant species until now toward understanding their physiological and metabolomics responses to global climate change. This review also discusses the following: (i) recent developments in plant metabolomics studies that can be applied to study and better understand the interactions of wet tropics plants with climatic stress, (ii) medicinal plants and isolated phytochemicals with structural diversity, and (iii) reported biological activities of crude extracts and isolated compounds.PMID:38611553 | DOI:10.3390/plants13071024

Plants (Basel). 2024 Mar 31;13(7):1003. doi: 10.3390/plants13071003.ABSTRACTContinuous spring cropping of Qingke (Hordeum viilgare L. var. nudum Hook. f.) results in a reduction in grain yield in the Xizang autonomous region. However, knowledge on the influence of continuous cropping on grain yield caused by reactive oxygen species (ROS)-induced stress remains scarce. A systematic comparison of the antioxidant defensive profile at seedling, tillering, jointing, flowering, and filling stages (T1 to T5) of Qingke was conducted based on a field experiment including 23-year continuous cropping (23y-CC) and control (the first year planted) treatments. The results reveal that the grain yield and superoxide anion (SOA) level under 23y-CC were significantly decreased (by 38.67% and 36.47%), when compared to the control. The hydrogen peroxide content under 23y-CC was 8.69% higher on average than under the control in the early growth stages. The higher ROS level under 23y-CC resulted in membrane lipid peroxidation (LPO) and accumulation of malondialdehyde (MDA) at later stages, with an average increment of 29.67% and 3.77 times higher than that in control plants. Qingke plants accumulated more hydrogen peroxide at early developmental stages due to the partial conversion of SOA by glutathione (GSH) and superoxide dismutase (SOD) and other production pathways, such as the glucose oxidase (GOD) and polyamine oxidase (PAO) pathways. The reduced regeneration ability due to the high oxidized glutathione (GSSG) to GSH ratio resulted in GSH deficiency while the reduction in L-galactono-1,4-lactone dehydrogenase (GalLDH) activity in the AsA biosynthesis pathway, higher enzymatic activities (including ascorbate peroxidase, APX; and ascorbate oxidase, AAO), and lower activities of monodehydroascorbate reductase (MDHAR) all led to a lower AsA content under continuous cropping. The lower antioxidant capacity due to lower contents of antioxidants such as flavonoids and tannins, detected through both physiological measurement and metabolomics analysis, further deteriorated the growth of Qingke through ROS stress under continuous cropping. Our results provide new insights into the manner in which ROS stress regulates grain yield in the context of continuous Qingke cropping.PMID:38611531 | DOI:10.3390/plants13071003

Plants (Basel). 2024 Mar 27;13(7):969. doi: 10.3390/plants13070969.ABSTRACTIn the context of climate change and the reduction of mineral nitrogen (N) inputs applied to the field, winter oilseed rape (WOSR) will have to cope with low-N conditions combined with water limitation periods. Since these stresses can significantly reduce seed yield and seed quality, maintaining WOSR productivity under a wide range of growth conditions represents a major goal for crop improvement. N metabolism plays a pivotal role during the metabolic acclimation to drought in Brassica species by supporting the accumulation of osmoprotective compounds and the source-to-sink remobilization of nutrients. Thus, N deficiency could have detrimental effects on the acclimation of WOSR to drought. Here, we took advantage of a previously established experiment to evaluate the metabolic acclimation of WOSR during 14 days of drought, followed by 8 days of rehydration under high- or low-N fertilization regimes. For this purpose, we selected three leaf ranks exhibiting contrasted sink/source status to perform absolute quantification of plant central metabolites. Besides the well-described accumulation of proline, we observed contrasted accumulations of some "respiratory" amino acids (branched-chain amino acids, lysineand tyrosine) in response to drought under high- and low-N conditions. Drought also induced an increase in sucrose content in sink leaves combined with a decrease in source leaves. N deficiency strongly decreased the levels of major amino acids and subsequently the metabolic response to drought. The drought-rehydration sequence identified proline, phenylalanine, and tryptophan as valuable metabolic indicators of WOSR water status for sink leaves. The results were discussed with respect to the metabolic origin of sucrose and some amino acids in sink leaves and the impact of drought on source-to-sink remobilization processes depending on N nutrition status. Overall, this study identified major metabolic signatures reflecting a similar response of oilseed rape to drought under low- and high-N conditions.PMID:38611498 | DOI:10.3390/plants13070969

Plants (Basel). 2024 Mar 23;13(7):930. doi: 10.3390/plants13070930.ABSTRACTOlive quick decline syndrome (OQDS) is a devastating plant disease caused by the bacterium Xylella fastidiosa (Xf). Exploratory missions in the Salento area led to the identification of putatively Xf-resistant olive trees (putatively resistant plants, PRPs) which were pauci-symptomatic or asymptomatic infected plants belonging to different genetic clusters in orchards severely affected by OQDS. To investigate the defense strategies employed by these PRPs to contrast Xf infection, the PRPs were analyzed for the anatomy and histology of xylem vessels, patterns of Xf distribution in host tissues (by the fluorescent in situ hybridization technique-FISH) and the presence of secondary metabolites in stems. The xylem vessels of the PRPs have an average diameter significantly lower than that of susceptible plants for each annual tree ring studied. The histochemical staining of xylem vessels highlighted an increase in the lignin in the parenchyma cells of the medullary rays of the wood. The 3D images obtained from FISH-LSM (laser scanning microscope) revealed that, in the PRPs, Xf cells mostly appeared as individual cells or as small aggregates; in addition, these bacterial cells looked to be incorporated in the autofluorescence signal of gels and phenolic compounds regardless of hosts' genotypes. In fact, the metabolomic data from asymptomatic PRP stems showed a significant increase in compounds like salicylic acid, known as a signal molecule which mediates host responses upon pathogen infection, and luteolin, a naturally derived flavonoid compound with antibacterial properties and with well-known anti-biofilm effects. Findings indicate that the xylem vessel geometry together with structural and chemical defenses are among the mechanisms operating to control Xf infection and may represent a common resistance trait among different olive genotypes.PMID:38611461 | DOI:10.3390/plants13070930

Plants (Basel). 2024 Mar 22;13(7):925. doi: 10.3390/plants13070925.ABSTRACTPotato Fusarium Wilt is a soil-borne fungal disease that can seriously harm potatoes throughout their growth period and occurs at different degrees in major potato-producing areas in China. To reduce the use of chemical agents and improve the effect of biocontrol agents, the inhibitory effects of the fermentation broth of Bacillus subtilis ZWZ-19 (B) and Trichoderma asperellum PT-29 (T) on Fusarium oxysporum were compared under single-culture and co-culture conditions. Furthermore, metabolomic analysis of the fermentation broths was conducted. The results showed that the inhibitory effect of the co-culture fermentation broth with an inoculation ratio of 1:1 (B1T1) was better than that of the separately cultured fermentation broths and had the best control effect in a potted experiment. Using LC-MS analysis, 134 metabolites were determined and classified into different types of amino acids. Furthermore, 10 metabolic pathways had the most significant variations, and 12 were related to amino acid metabolism in the KEGG analysis. A correlation analysis of the 79 differential metabolites generated through the comprehensive comparison between B, T, and B1T1 was conducted, and the results showed that highly abundant amino acids in B1T1 were correlated with amino acids in B, but not in T.PMID:38611455 | DOI:10.3390/plants13070925

Foods. 2024 Apr 7;13(7):1121. doi: 10.3390/foods13071121.ABSTRACTEpigallocatechin-3-gallate (EGCG) is a main bioactive constituent in green tea. Being a redox-active polyphenol, high-dose EGCG exhibits pro-oxidative activity and could cause liver injury. L-theanine is a unique non-protein amino acid in green tea and could provide liver-protective effects. The purpose of this study was to investigate the hepatoprotective effects of L-theanine on EGCG-induced liver injury and the underlying mechanisms. A total of 300 mg/kg L-theanine was administrated to ICR mice for 7 days. Then, the acute liver injury model was established through intragastric administration of 1000 mg/kg EGCG. Pretreatment with L-theanine significantly alleviated the oxidative stress and inflammatory response caused by high-dose EGCG through modulation of Nrf2 signaling and glutathione homeostasis. Furthermore, metabolomic results revealed that L-theanine protects mice from EGCG-induced liver injury mainly through the regulation of amino acid metabolism, especially tryptophan metabolism. These findings could provide valuable insights into the potential therapeutic applications of L-theanine and highlight the importance of the interactions between dietary components.PMID:38611425 | DOI:10.3390/foods13071121

Foods. 2024 Apr 3;13(7):1104. doi: 10.3390/foods13071104.ABSTRACTJam is a popular traditional and modern food product for daily consumption. However, the benefits of mixed jams over single-fruit jams have not been thoroughly explored, with analyses limited to superficial indices. In this study, Xinjiang special Morus nigra L. and Prunus domestica L. were used as raw materials to prepare single-fruit and mixed jams, and their differences in antioxidants, organoleptic qualities, pH, texture, and color were analyzed. The dynamics of metabolites before and after thermal processing were assessed using untargeted metabolomics. The results indicate that the main metabolites were flavonoids, terpenoids, amino acids, phenolic acids, and carbohydrates. Flavonoid metabolites changed significantly after thermal processing, with 40 up-regulated and 13 down-regulated. During storage, polyphenols were the prominent differential metabolites, with fifty-four down-regulated and one up-regulated. Volatile aroma components were analyzed using gas chromatography-ion mobility spectrometry (GC-IMS); the aroma components E-2-hexenal, E-2-pentenal, 3-methylbutanal, 1-penten-3-ol, tetrahydro-linalool, 1-penten-3-one, hexyl propionate, isoamyl acetate, α-pinene, and propionic acid in mixed jam were significantly higher than in single-fruit jam. In this study, untargeted metabolomics and GC-IMS were used to provide a more comprehensive and in-depth evaluation system for jam analysis.PMID:38611408 | DOI:10.3390/foods13071104

Foods. 2024 Apr 1;13(7):1084. doi: 10.3390/foods13071084.ABSTRACTFunctional foods have potential health benefits for humans. Lotus seeds (LS) as functional foods have excellent antioxidant activities. However, the differences in chemical composition of different LS cultivars may affect their antioxidant activities. This study comprehensively analyzed the differences among five LS cultivars based on metabolomics and further revealed the effects of metabolites on antioxidant activities by correlation analysis. A total of 125 metabolites were identified in LS using UPLC-Q/TOF-MS. Then, 15 metabolites were screened as differential metabolites of different LS cultivars by chemometrics. The antioxidant activities of LS were evaluated by DPPH•, FRAP, and ABTS•+ assays. The antioxidant activities varied among different LS cultivars, with the cultivar Taikong 66 showing the highest antioxidant activities. The correlation analysis among metabolites and antioxidant activities highlighted the important contribution of phenolics and alkaloids to the antioxidant activities of LS. Particularly, 11 metabolites such as p-coumaric acid showed significant positive correlation with antioxidant activities. Notably, 6 differential metabolites screened in different LS cultivars showed significant effects on antioxidant activities. These results revealed the important effects of phytochemicals on the antioxidant activities of different LS cultivars. This study provided evidence for the health benefits of different LS cultivars.PMID:38611388 | DOI:10.3390/foods13071084

Foods. 2024 Apr 1;13(7):1080. doi: 10.3390/foods13071080.ABSTRACTChrysanthemum tea, a typical health tea with the same origin as medicine and food, is famous for its unique health benefits and flavor. The taste and sensory quality of chrysanthemum (Juhua) tea are mainly determined by secondary metabolites. Therefore, the present research adopted untargeted metabolomics combined with an electronic tongue system to analyze the correlation between the metabolite profiles and taste characteristics of different varieties of chrysanthemum tea. The results of sensory evaluation showed that there were significant differences in the sensory qualities of five different varieties of chrysanthemum tea, especially bitterness and astringency. The results of principal component analysis (PCA) indicated that there were significant metabolic differences among the five chrysanthemum teas. A total of 1775 metabolites were identified by using untargeted metabolomics based on UPLC-Q-TOF/MS analysis. According to the variable importance in projection (VIP) values of the orthogonal projections to latent structures discriminant analysis (OPLS-DA), 143 VIP metabolites were found to be responsible for metabolic changes between Huangju and Jinsi Huangju tea; among them, 13 metabolites were identified as the key metabolites of the differences in sensory quality between them. Kaempferol, luteolin, genistein, and some quinic acid derivatives were correlated with the "astringency" attributes. In contrast, l-(-)-3 phenyllactic acid and L-malic acid were found to be responsible for the "bitterness" and "umami" attributes in chrysanthemum tea. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the flavonoid and flavonol biosynthesis pathways had important effects on the sensory quality of chrysanthemum tea. These findings provide the theoretical basis for understanding the characteristic metabolites that contribute to the distinctive sensory qualities of chrysanthemum tea.PMID:38611384 | DOI:10.3390/foods13071080

Foods. 2024 Mar 29;13(7):1047. doi: 10.3390/foods13071047.ABSTRACTFresh-cut processing is a good strategy to enhance the commercialization of peaches and nectarines, which easily deteriorate during low-temperature storage mostly due to the occurrence of chilling injury. Although several studies have been performed to improve the shelf-life of fresh-cut stone fruit, the achievement of high-quality fresh-cut peaches and nectarines still constitutes a challenge. The present study aimed to gain insights into the evolution of the postharvest quality of fresh-cut nectarines (Prunus persica L. Batsch) Big Bang, cold-stored at two different storage temperatures (4 and 8 °C) for up to 10 days. Several aspects influencing the quality traits (sensory and postharvest quality parameters; the profile of phenolic and volatile organic compounds (VOCs)) were explored to predict the marketable life of the fresh-cut nectarines. The respiration rate was higher in samples stored at 4 °C, while the browning process was more evident in fruit stored at 8 °C. Partial Least Squares Regression performed on VOCs showed that samples stored at 4 °C and 8 °C presented a different time evolution during the experiment and the trajectories depended on the interaction between time and temperature. Moreover, Multiple Linear Regression analysis discovered that the 17 VOCs affected by the storage conditions seemed to suggest that no chilling injury was detected for nectarines Big Bang. In conclusion, this approach could also be used with other nectarine cultivars and/or different stone fruits.PMID:38611352 | DOI:10.3390/foods13071047

Foods. 2024 Mar 28;13(7):1031. doi: 10.3390/foods13071031.ABSTRACTCocoa beans (Theobroma cacao L.) can be used for craft chocolate production, which arouses consumer interest due to their perceived better quality. This study aimed to evaluate the chemical profile of 80% artisanal chocolate samples produced with cocoa beans subjected to different maturation conditions. In the first maturation process, beans were matured under no-oxygen conditions, and in the second, the toasted beans were matured in oak barrels. The volatile compounds of the chocolate samples were extracted by the solid-phase microextraction method in headspace mode and analyzed by gas chromatography/mass spectrometer. The non-volatile compounds were extracted with methanol and analyzed through paper spray mass spectrometry. Overall, 35 volatile compounds belonging to different chemical classes (acids, alcohols, aldehydes, ketones, esters, and pyrazines) were identified, such as propanoic acid and butane-2,3-diol. In addition, 37 non-volatile compounds, such as procyanidin A pentoside and soyasaponin B, were listed. Tannins, flavonoids, and phenylpropanoids were the main chemical classes observed, varying between the two samples analyzed. Therefore, it was possible to verify that maturation conditions affected the metabolomic profile of the 80% artisanal chocolate samples, being able to influence the sensory characteristics and bioactive compounds profile. Given these results, the sensory evaluation of these chocolates is suggested as the next step.PMID:38611338 | DOI:10.3390/foods13071031

Foods. 2024 Mar 26;13(7):1006. doi: 10.3390/foods13071006.ABSTRACTThis study investigates the impact of urea and β-GP on the growth of Streptococcus thermophilus S-3, a bacterium commonly used in industrial fermentation processes. Through a series of growth experiments, transcriptome, metabolome, and omics-based analyses, the research demonstrates that both urea and β-GP can enhance the biomass of S. thermophilus, with urea showing a more significant effect. The optimal urea concentration for growth was determined to be 3 g/L in M17 medium. The study also highlights the metabolic pathways influenced by urea and β-GP, particularly the galactose metabolism pathway, which is crucial for cell growth when lactose is the substrate. The integration of omics data into the genome-scale metabolic model of S. thermophilus, iCH502, allowed for a more accurate prediction of metabolic fluxes and growth rates. The study concludes that urea can serve as a viable substitute for β-GP in the cultivation of S. thermophilus, offering potential cost and efficiency benefits in industrial fermentation processes. The findings are supported by validation experiments with 11 additional strains of S. thermophilus, which showed increased biomass in UM17 medium.PMID:38611312 | DOI:10.3390/foods13071006

Cancers (Basel). 2024 Apr 5;16(7):1418. doi: 10.3390/cancers16071418.ABSTRACTAdvanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919) and the matching cisplatin-resistant (R) sublines were used. A set of functional assays was used to perform a metabolic screening on the cells. In comparison to the parental sublines, a tendency was observed towards an exacerbated glycolytic metabolism in the cisplatin-resistant T24 and HT1376 cells; this glycolytic phenotype was particularly evident for the HT1376/HT1376R pair, for which the cisplatin resistance ratio was higher. HT1376R cells showed decreased basal respiration and oxygen consumption associated with ATP production; in accordance, the extracellular acidification rate was also higher in the resistant subline. Glycolytic rate assay confirmed that these cells presented higher basal glycolysis, with an increase in proton efflux. While the results of real-time metabolomics seem to substantiate the manifestation of the Warburg phenotype in HT1376R cells, a shift towards distinct metabolic pathways involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. On the other hand, KU1919R cells seem to engage in a metabolic rewiring, recovering their preference for oxidative phosphorylation. In conclusion, cisplatin-resistant UBC cells seem to display deep metabolic alterations surpassing the Warburg effect, which likely depend on the molecular signature of each cell line.PMID:38611096 | DOI:10.3390/cancers16071418

Cancers (Basel). 2024 Mar 23;16(7):1259. doi: 10.3390/cancers16071259.ABSTRACTThe vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50-70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1β, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.PMID:38610937 | DOI:10.3390/cancers16071259

Nat Commun. 2024 Apr 12;15(1):3175. doi: 10.1038/s41467-024-47581-1.ABSTRACTAlthough papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.PMID:38609408 | DOI:10.1038/s41467-024-47581-1

Signal Transduct Target Ther. 2024 Apr 12;9(1):98. doi: 10.1038/s41392-024-01796-2.ABSTRACTEvidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (β) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor β. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.PMID:38609366 | DOI:10.1038/s41392-024-01796-2