PubMed

Nutrients. 2023 Feb 27;15(5):1185. doi: 10.3390/nu15051185.ABSTRACTRoux-en-Y Gastric bypass (RYGB) promotes improvement in type 2 diabetes (T2D) shortly after surgery, with metabolic mechanisms yet to be elucidated. This study aimed to investigate the relationship between food intake, tryptophan metabolism, and gut microbiota on the glycemic control of obese T2D women after RYGB surgery. Twenty T2D women who underwent RYGB were evaluated before and three months after surgery. Food intake data were obtained by a seven-day food record and a food frequency questionnaire. Tryptophan metabolites were determined by untargeted metabolomic analysis, and the gut microbiota was determined by 16S rRNA sequencing. The glycemic outcomes were fasting blood glucose, HbA1C, HOMA-IR, and HOMA-beta. Linear regression models were applied to assess the associations between the changes in food intake, tryptophan metabolism, and gut microbiota on glycemic control after RYGB. All variables changed after RYGB (p < 0.05), except for tryptophan intake. Jointly, the variation in red meat intake, plasma indole-3-acetate, and Dorea longicatena was associated with postoperative HOMA-IR {R2 0.80, R2 adj 0.74; p < 0.01}. Red meat intake decreased three months after bariatric surgery while indole-3-acetate and Dorea longicatena increased in the same period. These combined variables were associated with better insulin resistance in T2D women after RYGB.PMID:36904185 | DOI:10.3390/nu15051185

Nutrients. 2023 Feb 24;15(5):1149. doi: 10.3390/nu15051149.ABSTRACTAcute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.PMID:36904149 | DOI:10.3390/nu15051149

Nutrients. 2023 Feb 24;15(5):1143. doi: 10.3390/nu15051143.ABSTRACTProtein-energy malnutrition still impacts children's growth and development. We investigated the prolonged effects of egg supplementation on growth and microbiota in primary school children. For this study, 8-14-year-old students (51.5% F) in six rural schools in Thailand were randomly assigned into three groups: (1) whole egg (WE), consuming 10 additional eggs/week (n = 238) (n = 238); (2) protein substitute (PS), consuming yolk-free egg substitutes equivalent to 10 eggs/week (n = 200); and (3) control group (C, (n = 197)). The outcomes were measured at week 0, 14, and 35. At the baseline, 17% of the students were underweight, 18% were stunted, and 13% were wasted. At week 35, compared to the C group the weight and height difference increased significantly in the WE group (3.6 ± 23.5 kg, p < 0.001; 5.1 ± 23.2 cm, p < 0.001). No significant differences in weight or height were observed between the PS and C groups. Significant decreases in atherogenic lipoproteins were observed in the WE, but not in PS group. HDL-cholesterol tended to increase in the WE group (0.02 ± 0.59 mmol/L, ns). The bacterial diversity was similar among the groups. The relative abundance of Bifidobacterium increased by 1.28-fold in the WE group compared to the baseline and differential abundance analysis which indicated that Lachnospira increased and Varibaculum decreased significantly. In conclusion, prolonged whole egg supplementation is an effective intervention to improve growth, nutritional biomarkers, and gut microbiota with unaltered adverse effects on blood lipoproteins.PMID:36904143 | DOI:10.3390/nu15051143

Nutrients. 2023 Feb 22;15(5):1100. doi: 10.3390/nu15051100.ABSTRACTHuman milk (HM) is a complex biofluid containing a wide cell variety including epithelial cells and leukocytes. However, the cellular compositions and their phenotypic properties over the course of lactation are poorly understood. The aim of this preliminary study was to characterize the cellular metabolome of HM over the course of lactation. Cells were isolated via centrifugation and the cellular fraction was characterized via cytomorphology and immunocytochemical staining. Cell metabolites were extracted and analyzed using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QqTOF-MS) in the positive and negative electrospray ionization modes. Immunocytochemical analysis revealed a high variability of the number of detected cells with relative median abundances of 98% of glandular epithelial cells, 1% of leukocytes, and 1% of keratinocytes. Significant correlations between the milk postnatal age with percentage of epithelial cells and leukocytes, and with total cell count were observed. Results from the Hierarchical Cluster Analysis of immunocytochemical profiles were very similar to those observed in the analysis of the metabolomic profiles. In addition, metabolic pathway analysis showed alterations in seven metabolic pathways correlating with postnatal age. This work paves the way for future investigations on changes in the metabolomic fraction of the cellular compartment of HM.PMID:36904100 | DOI:10.3390/nu15051100

Plants (Basel). 2023 Mar 3;12(5):1163. doi: 10.3390/plants12051163.ABSTRACTThe rac-GR24, an artificial analog of strigolactone, is known for its roles in inhibiting branches, and previous studies have reported that it has a certain mechanism to relieve abiotic stress, but the underlying metabolic mechanisms of mitigation for drought-induced remain unclear. Therefore, the objectives of this study were to identify associated metabolic pathways that are regulated by rac-GR24 in alfalfa (Medicago sativa L.) and to determine the metabolic mechanisms of rac-GR24 that are involved in drought-induced root exudate. The alfalfa seedling WL-712 was treated with 5% PEG to simulate drought, and rac-GR24 at a concentration of 0.1 µM was sprayed. After three days of treatment, root secretions within 24 h were collected. Osmotic adjustment substances and antioxidant enzyme activities were measured as physiological indicators, while LS/MS was performed to identify metabolites regulated by rac-GR24 of root exudate under drought. The results demonstrated that rac-GR24 treatment could alleviate the negative effects from drought-induced on alfalfa root, as manifested by increased osmotic adjustment substance content, cell membrane stability, and antioxidant enzyme activities. Among the 14 differential metabolites, five metabolites were uniquely downregulated in plants in rac-GR24 treatment. In addition, rac-GR24 could relieve drought-induced adverse effects on alfalfa through metabolic reprogramming in the pathways of the TCA cycle, pentose phosphate, tyrosine metabolism, and the purine pathway. This study indicated that rac-GR24 could improve the drought resistance of alfalfa by influencing the components of root exudates.PMID:36904026 | DOI:10.3390/plants12051163

Plants (Basel). 2023 Mar 2;12(5):1137. doi: 10.3390/plants12051137.ABSTRACTProteins play an essential regulatory role in the innate immune response of host plants following elicitation by either biotic or abiotic stresses. Isonitrosoacetophenone (INAP), an unusual oxime-containing stress metabolite, has been investigated as a chemical inducer of plant defence responses. Both transcriptomic and metabolomic studies of various INAP-treated plant systems have provided substantial insight into this compound's defence-inducing and priming capabilities. To complement previous 'omics' work in this regard, a proteomic approach of time-dependent responses to INAP was followed. As such, Nicotiana tabacum (N. tabacum) cell suspensions were induced with INAP and changes monitored over a 24-h period. Protein isolation and proteome analysis at 0, 8, 16 and 24 h post-treatment were performed using two-dimensional electrophoresis followed by the gel-free eight-plex isobaric tags for relative and absolute quantitation (iTRAQ) based on liquid chromatography and mass spectrometry. Of the identified differentially abundant proteins, 125 were determined to be significant and further investigated. INAP treatment elicited changes to the proteome that affected proteins from a wide range of functional categories: defence, biosynthesis, transport, DNA and transcription, metabolism and energy, translation and signalling and response regulation. The possible roles of the differentially synthesised proteins in these functional classes are discussed. Results indicate up-regulated defence-related activity within the investigated time period, further highlighting a role for proteomic changes in priming as induced by INAP treatment.PMID:36903995 | DOI:10.3390/plants12051137

Plants (Basel). 2023 Mar 2;12(5):1121. doi: 10.3390/plants12051121.ABSTRACTRhythmic exposure to moonlight has been shown to affect animal behavior, but its effects on plants, often observed in lunar agriculture, have been doubted and often regarded as myth. Consequently, lunar farming practices are not well scientifically supported, and the influence of this conspicuous environmental factor, the moon, on plant cell biology has hardly been investigated. We studied the effect of full moonlight (FML) on plant cell biology and examined changes in genome organization, protein and primary metabolite profiles in tobacco and mustard plants and the effect of FML on the post-germination growth of mustard seedlings. Exposure to FML was accompanied by a significant increase in nuclear size, changes in DNA methylation and cleavage of the histone H3 C-terminal region. Primary metabolites associated with stress were significantly increased along with the expression of stress-associated proteins and the photoreceptors phytochrome B and phototropin 2; new moon experiments disproved the light pollution effect. Exposure of mustard seedlings to FML enhanced growth. Thus, our data show that despite the low-intensity light emitted by the moon, it is an important environmental factor perceived by plants as a signal, leading to alteration in cellular activities and enhancement of plant growth.PMID:36903981 | DOI:10.3390/plants12051121

Plants (Basel). 2023 Mar 1;12(5):1096. doi: 10.3390/plants12051096.ABSTRACTRhizosphere microorganisms can help plants absorb nutrients, coordinate their growth, and improve their environmental adaptability. Coumarin can act as a signaling molecule that regulates the interaction between commensals, pathogens, and plants. In this study, we elucidate the effect of coumarin on plant root microorganisms. To provide a theoretical basis for the development of coumarin-derived compounds as biological pesticides, we determined the effect of coumarin on the root secondary metabolism and rhizosphere microbial community of annual ryegrass (Lolium multiflorum Lam.). We observed that a 200 mg/kg coumarin treatment had a negligible effect on the rhizosphere soil bacterial species of the annual ryegrass rhizosphere, though it exhibited a significant effect on the abundance of bacteria in the rhizospheric microbial community. Under coumarin-induced allelopathic stress, annual ryegrass can stimulate the colonization of beneficial flora in the root rhizosphere; however, certain pathogenic bacteria, such as Aquicella species, also multiply in large numbers in such conditions, which may be one of the main reasons for a sharp decline in the annual ryegrass biomass production. Further, metabolomics analysis revealed that the 200 mg/kg coumarin treatment triggered the accumulation of a total of 351 metabolites, of which 284 were found to be significantly upregulated, while 67 metabolites were significantly downregulated in the T200 group (treated with 200 mg/kg coumarin) compared to the CK group (control group) (p < 0.05). Further, the differentially expressed metabolites were primarily associated with 20 metabolic pathways, including phenylpropanoid biosynthesis, flavonoid biosynthesis, glutathione metabolism, etc. We found significant alterations in the phenylpropanoid biosynthesis and purine metabolism pathways (p < 0.05). In addition, there were significant differences between the rhizosphere soil bacterial community and root metabolites. Furthermore, changes in the bacterial abundance disrupted the balance of the rhizosphere micro-ecosystem and indirectly regulated the level of root metabolites. The current study paves the way towards comprehensively understanding the specific relationship between the root metabolite levels and the abundance of the rhizosphere microbial community.PMID:36903956 | DOI:10.3390/plants12051096

Molecules. 2023 Feb 28;28(5):2242. doi: 10.3390/molecules28052242.ABSTRACTGenistin, an isoflavone, has been reported to have multiple activities. However, its improvement of hyperlipidemia is still unclear, and the same is true with regard to its mechanism. In this study, a high-fat diet (HFD) was used to induce a hyperlipidemic rat model. The metabolites of genistin in normal and hyperlipidemic rats were first identified to cause metabolic differences with Ultra-High-Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS). The relevant factors were determined via ELISA, and the pathological changes of liver tissue were examined via H&E staining and Oil red O staining, which evaluated the functions of genistin. The related mechanism was elucidated through metabolomics and Spearman correlation analysis. The results showed that 13 metabolites of genistin were identified in plasma from normal and hyperlipidemic rats. Of those metabolites, seven were found in normal rat, and three existed in two models, with those metabolites being involved in the reactions of decarbonylation, arabinosylation, hydroxylation, and methylation. Three metabolites, including the product of dehydroxymethylation, decarbonylation, and carbonyl hydrogenation, were identified in hyperlipidemic rats for the first time. Accordingly, the pharmacodynamic results first revealed that genistin could significantly reduce the level of lipid factors (p < 0.05), inhibited lipid accumulation in the liver, and reversed the liver function abnormalities caused by lipid peroxidation. For metabolomics results, HFD could significantly alter the levels of 15 endogenous metabolites, and genistin could reverse them. Creatine might be a beneficial biomarker for the activity of genistin against hyperlipidemia, as revealed via multivariate correlation analysis. These results, which have not been reported in the previous literature, may provide the foundation for genistin as a new lipid-lowering agent.PMID:36903488 | DOI:10.3390/molecules28052242

Molecules. 2023 Feb 27;28(5):2223. doi: 10.3390/molecules28052223.ABSTRACTRipening time is known to drive the chemical and sensory profiles of dry meat products, thus potentially affecting the final quality of the product. Starting from these background conditions, the aim of this work was to shed light, for the first time, on the chemical modifications of a typical Italian PDO meat product-namely, Coppa Piacentina-during ripening, to find correlations between its sensory quality and the biomarker compounds related to the progress of ripening. The ripening time (from 60 to 240 days) was found to deeply modify the chemical composition of this typical meat product, providing potential biomarkers of both oxidative reactions and sensory attributes. The chemical analyses revealed that there is typically a significant decrease in the moisture content during ripening, likely due to increased dehydration. In addition, the fatty acid profile showed that the distribution of polyunsaturated fatty acids significantly (p < 0.05) decreased during ripening, because of their high susceptibility to oxidation and conversion to intermediate and secondary molecules. An untargeted metabolomics approach, coupled with unsupervised and supervised multivariate statistics, highlighted a significant impact (prediction scores > 1) of lipid oxidation during ripening time, with some metabolites (such as γ -glutamyl-peptides, hydroperoxy-fatty acids, and glutathione) being particularly discriminant in predicting the changes observed. The discriminant metabolites were coherent with the progressive increase of peroxide values determined during the entire ripening period. Finally, the sensory analysis outlined that the highest degree of ripening provided greater color intensity of the lean part, slice firmness, and chewing consistency, with glutathione and γ-glutamyl-glutamic acid establishing the highest number of significant correlations with the sensory attributes evaluated. Taken together, this work highlights the importance and validity of untargeted metabolomics coupled with sensory analysis to investigate the comprehensive chemical and sensory changes to dry meat during ripening.PMID:36903465 | DOI:10.3390/molecules28052223

Molecules. 2023 Feb 25;28(5):2166. doi: 10.3390/molecules28052166.ABSTRACTHair may be a potential biospecimen to discover biomarkers for Alzheimer's disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol/phosphate-buffered saline 50/50 (v/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD.PMID:36903413 | DOI:10.3390/molecules28052166

Molecules. 2023 Feb 24;28(5):2122. doi: 10.3390/molecules28052122.ABSTRACTOlive pomace (OP) represents one of the main by-products of olive oil production, which still contains high quantities of health-promoting bioactive compounds. In the present study, three batches of sun-dried OP were characterized for their profile in phenolic compounds (by HPLC-DAD) and in vitro antioxidant properties (ABTS, FRAP and DPPH assays) before (methanolic extracts) and after (aqueous extracts) their simulated in vitro digestion and dialysis. Phenolic profiles, and, accordingly, the antioxidant activities, showed significant differences among the three OP batches, and most compounds showed good bioaccessibility after simulated digestion. Based on these preliminary screenings, the best OP aqueous extract (OP-W) was further characterized for its peptide composition and subdivided into seven fractions (OP-F). The most promising OP-F (characterized for its metabolome) and OP-W samples were then assessed for their potential anti-inflammatory properties in ex vivo human peripheral mononuclear cells (PBMCs) triggered or not with lipopolysaccharide (LPS). The levels of 16 pro-and anti-inflammatory cytokines were measured in PBMC culture media by multiplex ELISA assay, whereas the gene expressions of interleukin-6 (IL-6), IL-10 and TNF-α were measured by real time RT-qPCR. Interestingly, OP-W and PO-F samples had a similar effect in reducing the expressions of IL-6 and TNF-α, but only OP-W was able to reduce the release of these inflammatory mediators, suggesting that the anti-inflammatory activity of OP-W is different from that of OP-F.PMID:36903372 | DOI:10.3390/molecules28052122

Molecules. 2023 Feb 22;28(5):2051. doi: 10.3390/molecules28052051.ABSTRACTCancer therapies use different compounds of synthetic and natural origin. However, despite some positive results, relapses are common, as standard chemotherapy regimens are not fully capable of completely eradicating cancer stem cells. While vinblastine is a common chemotherapeutic agent in the treatment of blood cancers, the development of vinblastine resistance is often observed. Here, we performed cell biology and metabolomics studies to investigate the mechanisms of vinblastine resistance in P3X63Ag8.653 murine myeloma cells. Treatment with low doses of vinblastine in cell media led to the selection of vinblastine-resistant cells and the acquisition of such resistance in previously untreated, murine myeloma cells in culture. To determine the mechanistic basis of this observation, we performed metabolomic analyses of resistant cells and resistant drug-induced cells in a steady state, or incubation with stable isotope-labeled tracers, namely, 13C 15N-amino acids. Taken together, these results indicate that altered amino acid uptake and metabolism could contribute to the acquisition of vinblastine resistance in blood cancer cells. These results will be useful for further research on human cell models.PMID:36903299 | DOI:10.3390/molecules28052051

J Clin Med. 2023 Feb 23;12(5):1799. doi: 10.3390/jcm12051799.ABSTRACTCardiac diseases form the lion's share of the global disease burden, owing to the paradigm shift to non-infectious diseases from infectious ones. The prevalence of CVDs has nearly doubled, increasing from 271 million in 1990 to 523 million in 2019. Additionally, the global trend for the years lived with disability has doubled, increasing from 17.7 million to 34.4 million over the same period. The advent of precision medicine in cardiology has ignited new possibilities for individually personalized, integrative, and patient-centric approaches to disease prevention and treatment, incorporating the standard clinical data with advanced "omics". These data help with the phenotypically adjudicated individualization of treatment. The major objective of this review was to compile the evolving clinically relevant tools of precision medicine that can help with the evidence-based precise individualized management of cardiac diseases with the highest DALY. The field of cardiology is evolving to provide targeted therapy, which is crafted as per the "omics", involving genomics, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics, for deep phenotyping. Research for individualizing therapy in heart diseases with the highest DALY has helped identify novel genes, biomarkers, proteins, and technologies to aid early diagnosis and treatment. Precision medicine has helped in targeted management, allowing early diagnosis, timely precise intervention, and exposure to minimal side effects. Despite these great impacts, overcoming the barriers to implementing precision medicine requires addressing the economic, cultural, technical, and socio-political issues. Precision medicine is proposed to be the future of cardiovascular medicine and holds the potential for a more efficient and personalized approach to the management of cardiovascular diseases, contrary to the standardized blanket approach.PMID:36902588 | DOI:10.3390/jcm12051799

Int J Mol Sci. 2023 Mar 6;24(5):5044. doi: 10.3390/ijms24055044.ABSTRACTGrape hyacinth (Muscari spp.) is a famous bulbous blue flower; however, few bicolor varieties are available in the market. Therefore, the discovery of bicolor varieties and understanding of their mechanisms are crucial to the breeding of new varieties. In this study, we report a significant bicolor mutant with white upper and violet lower portions, with both parts belonging to a single raceme. Ionomics showed that pH and metal element contents were not responsible for the bicolor formation. Targeted metabolomics illustrated that the content of the 24 color-related compounds was significantly lower in the upper part than that in the lower part. Moreover, full-length transcriptomics combined with second-generation transcriptomics revealed 12,237 differentially expressed genes in which anthocyanin synthesis gene expression of the upper part was noted to be significantly lower than that of the lower part. Transcription factor differential expression analysis was used to describe the presence of a pair of MaMYB113a/b sequences, with low levels of expression in the upper part and high expression in the lower part. Furthermore, tobacco transformation confirmed that overexpression of MaMYB113a/b can promote anthocyanin accumulation in tobacco leaves. Accordingly, the differential expression of MaMYB113a/b contributes the formation of a bicolor mutant in Muscari latifolium.PMID:36902472 | DOI:10.3390/ijms24055044

Int J Mol Sci. 2023 Mar 5;24(5):4991. doi: 10.3390/ijms24054991.ABSTRACTDuring bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca2+]i transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.PMID:36902420 | DOI:10.3390/ijms24054991

Int J Mol Sci. 2023 Mar 4;24(5):4960. doi: 10.3390/ijms24054960.ABSTRACTAlzheimer's disease (AD) is an aging-related neurodegenerative disease, leading to the progressive loss of memory and other cognitive functions. As there is still no cure for AD, the growth in the number of susceptible individuals represents a major emerging threat to public health. Currently, the pathogenesis and etiology of AD remain poorly understood, while no efficient treatments are available to slow down the degenerative effects of AD. Metabolomics allows the study of biochemical alterations in pathological processes which may be involved in AD progression and to discover new therapeutic targets. In this review, we summarized and analyzed the results from studies on metabolomics analysis performed in biological samples of AD subjects and AD animal models. Then this information was analyzed by using MetaboAnalyst to find the disturbed pathways among different sample types in human and animal models at different disease stages. We discuss the underlying biochemical mechanisms involved, and the extent to which they could impact the specific hallmarks of AD. Then we identify gaps and challenges and provide recommendations for future metabolomics approaches to better understand AD pathogenesis.PMID:36902391 | DOI:10.3390/ijms24054960

Int J Mol Sci. 2023 Mar 3;24(5):4941. doi: 10.3390/ijms24054941.ABSTRACTProspective studies have failed to establish a causal relationship between animal fat intake and cardiovascular diseases in humans. Furthermore, the metabolic effects of different dietary sources remain unknown. In this four-arm crossover study, we investigated the impact of consuming cheese, beef, and pork meat on classic and new cardiovascular risk markers (obtained from lipidomics) in the context of a healthy diet. A total of 33 young healthy volunteers (23 women/10 men) were assigned to one out of four test diets in a Latin square design. Each test diet was consumed for 14 days, with a 2-week washout. Participants received a healthy diet plus Gouda- or Goutaler-type cheeses, pork, or beef meats. Before and after each diet, fasting blood samples were withdrawn. A reduction in total cholesterol and an increase in high density lipoprotein particle size were detected after all diets. Only the pork diet upregulated plasma unsaturated fatty acids and downregulated triglycerides species. Improvements in the lipoprotein profile and upregulation of circulating plasmalogen species were also observed after the pork diet. Our study suggests that, within the context of a healthy diet rich in micronutrients and fiber, the consumption of animal products, in particular pork meat, may not induce deleterious effects, and reducing the intake of animal products should not be regarded as a way of reducing cardiovascular risk in young individuals.PMID:36902372 | DOI:10.3390/ijms24054941

Int J Mol Sci. 2023 Mar 3;24(5):4922. doi: 10.3390/ijms24054922.ABSTRACTSARS-CoV-2 infection is characterized by several clinical manifestations, ranging from the absence of symptoms to severe forms that necessitate intensive care treatment. It is known that the patients with the highest rate of mortality develop increased levels of proinflammatory cytokines, called the "cytokine storm", which is similar to inflammatory processes that occur in cancer. Additionally, SARS-CoV-2 infection induces modifications in host metabolism leading to metabolic reprogramming, which is closely linked to metabolic changes in cancer. A better understanding of the correlation between perturbed metabolism and inflammatory responses is necessary. We evaluated untargeted plasma metabolomics and cytokine profiling via 1H-NMR (proton nuclear magnetic resonance) and multiplex Luminex assay, respectively, in a training set of a limited number of patients with severe SARS-CoV-2 infection classified on the basis of their outcome. Univariate analysis and Kaplan-Meier curves related to hospitalization time showed that lower levels of several metabolites and cytokines/growth factors, correlated with a good outcome in these patients and these data were confirmed in a validation set of patients with similar characteristics. However, after the multivariate analysis, only the growth factor HGF, lactate and phenylalanine retained a significant prediction of survival. Finally, the combined analysis of lactate and phenylalanine levels correctly predicted the outcome of 83.3% of patients in both the training and the validation set. We highlighted that the cytokines and metabolites involved in COVID-19 patients' poor outcomes are similar to those responsible for cancer development and progression, suggesting the possibility of targeting them by repurposing anticancer drugs as a therapeutic strategy against severe SARS-CoV-2 infection.PMID:36902351 | DOI:10.3390/ijms24054922

Int J Mol Sci. 2023 Mar 3;24(5):4902. doi: 10.3390/ijms24054902.ABSTRACTToxoplasma gondii is an obligate protozoon that can infect all warm-blooded animals including humans. T. gondii afflicts one-third of the human population and is a detriment to the health of livestock and wildlife. Thus far, traditional drugs such as pyrimethamine and sulfadiazine used to treat T. gondii infection are inadequate as therapeutics due to relapse, long treatment period, and low efficacy in parasite clearance. Novel, efficacious drugs have not been available. Lumefantrine, as an antimalarial, is effective in killing T. gondii but has no known mechanism of action. We combined metabolomics with transcriptomics to investigate how lumefantrine inhibits T. gondii growth. We identified significant alternations in transcripts and metabolites and their associated functional pathways that are attributed to lumefantrine treatment. RH tachyzoites were used to infect Vero cells for three hours and subsequently treated with 900 ng/mL lumefantrine. Twenty-four hours post-drug treatment, we observed significant changes in transcripts associated with five DNA replication and repair pathways. Metabolomic data acquired through liquid chromatography-tandem mass spectrometry (LC-MS) showed that lumefantrine mainly affected sugar and amino acid metabolism, especially galactose and arginine. To investigate whether lumefantrine damages T. gondii DNA, we conducted a terminal transferase assay (TUNEL). TUNEL results showed that lumefantrine significantly induced apoptosis in a dose-dependent manner. Taken together, lumefantrine effectively inhibited T. gondii growth by damaging DNA, interfering with DNA replication and repair, and altering energy and amino acid metabolisms.PMID:36902335 | DOI:10.3390/ijms24054902