PubMed

Antioxidants (Basel). 2024 Feb 15;13(2):238. doi: 10.3390/antiox13020238.ABSTRACTThis study sought to optimize the ultrasonic-assisted extraction of polyphenolic compounds from unmature Ajwa date seeds (UMS), conduct untargeted metabolite identification and assess antioxidant and depigmenting activities. Response surface methodology (RSM) utilizing the Box-Behnken design (BBD) and artificial neural network (ANN) modeling was applied to optimize extraction conditions, including the ethanol concentration, extraction temperature and time. The determined optimal conditions comprised the ethanol concentration (62.00%), extraction time (29.00 min), and extraction temperature (50 °C). Under these conditions, UMS exhibited total phenolic content (TPC) and total flavonoid content (TFC) values of 77.52 ± 1.55 mgGAE/g and 58.85 ± 1.12 mgCE/g, respectively, with low relative standard deviation (RSD%) and relative standard error (RSE%). High-resolution mass spectrometry analysis unveiled the presence of 104 secondary metabolites in UMS, encompassing phenols, flavonoids, sesquiterpenoids, lignans and fatty acids. Furthermore, UMS demonstrated robust antioxidant activities in various cell-free antioxidant assays, implicating engagement in both hydrogen atom transfer and single electron transfer mechanisms. Additionally, UMS effectively mitigated tert-butyl hydroperoxide (t-BHP)-induced cellular reactive oxygen species (ROS) generation in a concentration-dependent manner. Crucially, UMS showcased the ability to activate mitogen-activated protein kinases (MAPKs) and suppress key proteins including tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and -2) and microphthalmia-associated transcription factor (MITF), which associated melanin production in MNT-1 cell. In summary, this study not only optimized the extraction process for polyphenolic compounds from UMS but also elucidated its diverse secondary metabolite profile. The observed antioxidant and depigmenting activities underscore the promising applications of UMS in skincare formulations and pharmaceutical developments.PMID:38397836 | DOI:10.3390/antiox13020238

Antioxidants (Basel). 2024 Feb 14;13(2):233. doi: 10.3390/antiox13020233.ABSTRACTSoil salinity is one of the adversity stresses plants face, and antioxidant defense mechanisms play an essential role in plant resistance. We investigated the effects of exogenous calcium on the antioxidant defense system in peanut seedling roots that are under salt stress by using indices including the transcriptome and absolute quantitative metabolome of flavonoids. Under salt stress conditions, the antioxidant defense capacity of enzymatic systems was weakened and the antioxidant capacity of the linked AsA-GSH cycle was effectively inhibited. In contrast, the ascorbate biosynthesis pathway and its upstream glycolysis metabolism pathway became active, which stimulated shikimate biosynthesis and the downstream phenylpropanoid metabolism pathway, resulting in an increased accumulation of flavonoids, which, as one of the antioxidants in the non-enzymatic system, provide hydroxyl radicals to scavenge the excess reactive oxygen species and maintain the plant's vital activities. However, the addition of exogenous calcium caused changes in the antioxidant defense system in the peanut root system. The activity of antioxidant enzymes and the antioxidant capacity of the AsA-GSH cycle were enhanced. Therefore, glycolysis and phenylpropanoid metabolism do not exert antioxidant function, and flavonoids were no longer synthesized. In addition, antioxidant enzymes and the AsA-GSH cycle showed a trade-off relationship with sugars and flavonoids.PMID:38397831 | DOI:10.3390/antiox13020233

Antioxidants (Basel). 2024 Feb 8;13(2):220. doi: 10.3390/antiox13020220.ABSTRACTPhospholipases (PL) A2 catalyzes the hydrolysis of membrane phospholipids and mostly generates arachidonic acid (AA). The enzyme 5-lipoxygenase (5-LOX) can metabolize AA to obtain inflammatory leukotrienes, whose biosynthesis highly depends on cPLA2 and 5-LOX activities. Formyl Peptide Receptor 2 (FPR2) belongs to a subfamily of class A GPCRs and is considered the most versatile FPRs isoform. Signaling triggered by FPR2 includes the activation of several downstream kinases and NADPH oxidase (NOX)-dependent ROS generation. In a metabolomic analysis we observed a significant increase in AA concentration in FPR2-stimulated lung cancer cell line CaLu-6. We analyzed cPLA2 phosphorylation and observed a time-dependent increase in cPLA2 Ser505 phosphorylation in FPR2-stimulated cells, which was prevented by the MEK inhibitor (PD098059) and the p38MAPK inhibitor (SB203580) and by blocking NOX function. Similarly, we demonstrated that phosphorylation of 5-LOX at Ser271 and Ser663 residues requires FPR2-dependent p38MAPK and ERKs activation. Moreover, we showed that 5-LOX Ser271 phosphorylation depends on a functional NOX expression. Our overall data demonstrate for the first time that FPR2-induced ERK- and p38MAPK-dependent phosphorylation/activation of cPLA2 and 5-LOX requires a functional NADPH oxidase. These findings represent an important step towards future novel therapeutic possibilities aimed at resolving the inflammatory processes underlying many human diseases.PMID:38397818 | DOI:10.3390/antiox13020220

Antioxidants (Basel). 2024 Feb 8;13(2):214. doi: 10.3390/antiox13020214.ABSTRACTUlcerative colitis is an inflammatory bowel disease with multiple pathogeneses. Here, we aimed to study the therapeutic role of ulinastatin (UTI), an anti-inflammatory bioagent, and its associated mechanisms in treating colitis. Dextran sulfate sodium was administrated to induce colitis in mice, and a subgroup of colitis mice was treated with UTI. The gut barrier defect and inflammatory manifestations of colitis were determined via histological and molecular experiments. In addition, transcriptomics, metagenomics, and metabolomics were employed to explore the possible mechanisms underlying the effects of UTI. We found that UTI significantly alleviated the inflammatory manifestations and intestinal barrier damage in the mice with colitis. Transcriptome sequencing revealed a correlation between the UTI treatment and JAK-STAT signaling pathway. UTI up-regulated the expression of SOCS1, which subsequently inhibited the phosphorylation of JAK2 and STAT3, thus limiting the action of inflammatory mediators. In addition, 16S rRNA sequencing illustrated that UTI maintained a more stable intestinal flora, protecting the gut from dysbiosis in colitis. Moreover, metabolomics analysis demonstrated that UTI indeed facilitated the production of some bile acids and short-chain fatty acids, which supported intestinal homeostasis. Our data provide evidence that UTI is effective in treating colitis and support the potential use of UTI treatment for patients with ulcerative colitis.PMID:38397811 | DOI:10.3390/antiox13020214

Antioxidants (Basel). 2024 Jan 29;13(2):170. doi: 10.3390/antiox13020170.ABSTRACTWith the gradual decline in freshwater resources, the space available for freshwater aquaculture is diminishing and the need to maximize saline water for aquaculture is increasing. This study aimed to elucidate the impact mechanisms of the disruption of the glutamate pathway on serum metabolism and ammonia excretion in crucian carp (Carassius auratus) under carbonate alkaline stress. A freshwater control group (C group), a 20 mmol/L NaHCO3 stress group (L group), and a 40 mmol/L NaHCO3 stress group (H group) were established. After 30 days of exposure, methionine sulfoximine (MSO) was injected to block the glutamate pathway metabolism, and the groups post-blocking were labeled as MC, ML, and MH. Ultra-high-performance liquid chromatography coupled with the quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics technique was employed to detect changes in the composition and content of crucian carp serum metabolites. Significant differential metabolites were identified, and related metabolic pathways were analyzed. The results revealed that, following the glutamate pathway blockade, a total of 228 differential metabolites (DMs) were identified in the three treatment groups. An enrichment analysis indicated significant involvement in glycerophospholipid metabolism, arachidonic acid metabolism, sphingolipid metabolism, purine metabolism, arginine and proline biosynthesis, pantothenate and CoA biosynthesis, glutathione metabolism, and fatty acid degradation, among other metabolic pathways. The results showed that ROS imbalances and L-arginine accumulation in crucian carp after the glutamate pathway blockade led to an increase in oxidative stress and inflammatory responses in vivo, which may cause damage to the structure and function of cell membranes. Crucian carp improves the body's antioxidant capacity and regulates cellular homeostasis by activating glutathione metabolism and increasing the concentration of phosphatidylcholine (PC) analogs. Additionally, challenges such as aggravated ammonia excretion obstruction and disrupted energy metabolism were observed in crucian carp, with the upregulation of purine metabolism alleviating ammonia toxicity and maintaining energy homeostasis through pantothenate and CoA biosynthesis as well as fatty acid degradation. This study elucidated the metabolic changes in crucian carp under carbonate alkaline stress after a glutamate pathway blockade at the cellular metabolism level and screened out the key metabolic pathways, which provide a scientific basis for further in-depth studies on the ammonia excretion of freshwater scleractinian fishes under saline and alkaline habitats at a later stage.PMID:38397768 | DOI:10.3390/antiox13020170

Foods. 2024 Feb 9;13(4):544. doi: 10.3390/foods13040544.ABSTRACTAdipose tissue is a crucial economically significant trait that significantly influences the meat quality and growth performance of domestic animals. To reveal the changes in adipose tissue metabolism during the growth of naturally grazing sheep, we evaluated the thickness, adipocyte morphology, fatty acid profile, and metabolite profile of subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (referred to as Mth-6, Mth-18, and Mth-30, respectively). The fat thickness and adipocyte number were significantly increased with the growth of the sheep (p < 0.05), and the increase of which from Mth-18 to Mth-30 was less than that from Mth-6 to Mth-18. Additionally, the alpha-linolenic acid metabolism was enhanced and fatty acid (FA) elongation increased with growth. The metabolomic analysis revealed 76 differentially expressed metabolites (DEMs) in the SAT in different growth stages. Interestingly, we observed elongation of FAs in lipids correlated with sheep growth. Furthermore, the expression of acylcarnitines was downregulated, and fatty acid amides, aspartic acid, acetic acid and phosphocholine were upregulated in Mth-18 and Mth-30 compared to Mth-6. Altogether, the study found that the difference in SAT in Mth-6 was great compared to Mth-18 and Mth-30. An increase in fat deposition via adipocyte proliferation with the growth of the sheep in naturally grazing. The DEMs of acylcarnitines, fatty acid amides, aspartic acid, acetic acid, and phosphocholine emerged as potential key regulators of adipose tissue metabolism. These findings illustrate the variation in and metabolic mechanism of sheep adipose tissue development under natural grazing, thus providing valuable insights into improving the edible quality of sheep meat and developing the mutton sheep industry.PMID:38397521 | DOI:10.3390/foods13040544

Biomolecules. 2024 Feb 19;14(2):241. doi: 10.3390/biom14020241.ABSTRACTThe serine peptidase CLPP is conserved among bacteria, chloroplasts, and mitochondria. In humans and mice, its loss causes Perrault syndrome, which presents with growth deficits, infertility, deafness, and ataxia. In the filamentous fungus Podospora anserina, CLPP loss leads to longevity. CLPP substrates are selected by CLPX, an AAA+ unfoldase. CLPX is known to target delta-aminolevulinic acid synthase (ALAS) to promote pyridoxal phosphate (PLP) binding. CLPX may also influence cofactor association with other enzymes. Here, the evaluation of P. anserina metabolomics highlighted a reduction in arginine/histidine levels. In Mus musculus cerebellum, reductions in arginine/histidine and citrulline occurred with a concomitant accumulation of the heme precursor protoporphyrin IX. This suggests that the increased biosynthesis of 5-carbon (C5) chain deltaALA consumes not only C4 succinyl-CoA and C1 glycine but also specific C5 delta amino acids. As enzymes responsible for these effects, the elevated abundance of CLPX and ALAS is paralleled by increased OAT (PLP-dependent, ornithine delta-aminotransferase) levels. Possibly as a consequence of altered C1 metabolism, the proteome profiles of P. anserina CLPP-null cells showed strong accumulation of a methyltransferase and two mitoribosomal large subunit factors. The reduced histidine levels may explain the previously observed metal interaction problems. As the main nitrogen-storing metabolite, a deficiency in arginine would affect the urea cycle and polyamine synthesis. Supplementation of arginine and histidine might rescue the growth deficits of CLPP-mutant patients.PMID:38397478 | DOI:10.3390/biom14020241

Biomolecules. 2024 Feb 17;14(2):235. doi: 10.3390/biom14020235.ABSTRACTAdrenal function is essential for survival and well-being of preterm babies. In addition to glucocorticoids, it has been hypothesized that C19-steroids (DHEA-metabolites) from the fetal zone of the adrenal gland may play a role as endogenous neuroprotective steroids. In 39 term-born (≥37 weeks gestational age), 42 preterm (30-36 weeks) and 51 early preterm (<30 weeks) infants 38 steroid metabolites were quantified by GC-MS in 24-h urinary samples. In each gestational age group, three distinctive cluster were identified by pattern analysis (k-means clustering). Individual steroidal fingerprints and clinical phenotype were analyzed at the 3rd day of life. Overall, the excretion rates of C21-steroids (glucocorticoid precursors, cortisol, and cortisone metabolites) were low (<99 μg/kg body weight/d) whereas the excretion rates of C19-steroids were up to 10 times higher. There was a shift to higher excretion rates of C19-steroids in both preterm groups compared to term infants but only minor differences in the distribution of C21-steroids. Comparable metabolic patterns were found between gestational age groups: Cluster 1 showed mild elevation of C21- and C19-steroids with the highest incidence of neonatal morbidities in term and severe intraventricular hemorrhage in early preterm infants. In cluster 2 lowest excretion in general was noted but no clinically unique phenotype. Cluster 3 showed highest elevation of C21-steroids and C19-steroids but no clinically unique phenotype. Significant differences in steroid metabolism between clusters are only partly reflected by gestational age and disease severity. In early preterm infants, higher excretion rates of glucocorticoids and their precursors were associated with severe cerebral hemorrhage. High excretion rates of C19-steroids in preterm infants may indicate a biological significance.PMID:38397473 | DOI:10.3390/biom14020235

Biomolecules. 2024 Feb 16;14(2):227. doi: 10.3390/biom14020227.ABSTRACTPlant cuticular wax forms a hydrophobic structure in the cuticle layer covering epidermis as the first barrier between plants and environments. Ammopiptanthus mongolicus, a leguminous desert shrub, exhibits high tolerances to multiple abiotic stress. The physiological, chemical, and transcriptomic analyses of epidermal permeability, cuticular wax metabolism and related gene expression profiles under osmotic stress in A. mongolicus leaves were performed. Physiological analyses revealed decreased leaf epidermal permeability under osmotic stress. Chemical analyses revealed saturated straight-chain alkanes as major components of leaf cuticular wax, and under osmotic stress, the contents of total wax and multiple alkane components significantly increased. Transcriptome analyses revealed the up-regulation of genes involved in biosynthesis of very-long-chain fatty acids and alkanes and wax transportation under osmotic stress. Weighted gene co-expression network analysis identified 17 modules and 6 hub genes related to wax accumulation, including 5 enzyme genes coding KCS, KCR, WAX2, FAR, and LACS, and an ABCG transporter gene. Our findings indicated that the leaf epidermal permeability of A. mongolicus decreased under osmotic stress to inhibit water loss via regulating the expression of wax-related enzyme and transporter genes, further promoting cuticular wax accumulation. This study provided new evidence for understanding the roles of cuticle lipids in abiotic stress tolerance of desert plants.PMID:38397464 | DOI:10.3390/biom14020227

Biomolecules. 2024 Feb 2;14(2):182. doi: 10.3390/biom14020182.ABSTRACTThe NAC family of transcription factors (TFs) is recognized as a significant group within the plant kingdom, contributing crucially to managing growth and development processes in plants, as well as to their response and adaptation to various environmental stressors. Ammopiptanthus mongolicus, a temperate evergreen shrub renowned for its remarkable resilience to low temperatures and drought stress, presents an ideal subject for investigating the potential involvement of NAC TFs in stress response mechanisms. Here, the structure, evolution, and expression profiles of NAC family TFs were analyzed systematically, and a cold and osmotic stress-induced member, AmNAC24, was selected and functionally characterized. A total of 86 NAC genes were identified in A. mongolicus, and these were divided into 15 groups. Up to 48 and 8 NAC genes were generated by segmental duplication and tandem duplication, respectively, indicating that segmental duplication is a predominant mechanism in the expansion of the NAC gene family in A. mongolicus. A considerable amount of NAC genes, including AmNAC24, exhibited upregulation in response to cold and osmotic stress. This observation is in line with the detection of numerous cis-acting elements linked to abiotic stress response in the promoters of A. mongolicus NAC genes. Subcellular localization revealed the nuclear residence of the AmNAC24 protein, coupled with demonstrable transcriptional activation activity. AmNAC24 overexpression enhanced the tolerance of cold and osmotic stresses in Arabidopsis thaliana, possibly by maintaining ROS homeostasis. The present study provided essential data for understanding the biological functions of NAC TFs in plants.PMID:38397419 | DOI:10.3390/biom14020182

Biomolecules. 2024 Jan 29;14(2):160. doi: 10.3390/biom14020160.ABSTRACTHolm oak (Quercus ilex) is considered to be one of the major structural elements of Mediterranean forests and the agrosilvopastoral Spanish "dehesa", making it an outstanding example of ecological and socioeconomic sustainability in forest ecosystems. The exotic Phytophthora cinnamomi is one of the most aggressive pathogens of woody species and, together with drought, is considered to be one of the main drivers of holm oak decline. The effect of and response to P. cinnamomi inoculation were studied in the offspring of mother trees from two Andalusian populations, Cordoba and Huelva. At the two locations, acorns collected from both symptomatic (damaged) and asymptomatic (apparently healthy) trees were sampled. Damage symptoms, mortality, and chlorophyll fluorescence were evaluated in seedlings inoculated under humid and drought conditions. The effect and response depended on the population and were more apparent in Huelva than in Cordoba. An integrated proteomic and metabolomic analysis revealed the involvement of different metabolic pathways in response to the pathogen in both populations, including amino acid metabolism pathways in Huelva, and terpenoid and flavonoid biosynthesis in Cordoba. However, no differential response was observed between seedlings inoculated under humid and drought conditions. A protective mechanism of the photosynthetic apparatus was activated in response to defective photosynthetic activity in inoculated plants, which seemed to be more efficient in the Cordoba population. In addition, enzymes and metabolites of the phenylpropanoid and flavonoid biosynthesis pathways may have conferred higher resistance in the Cordoba population. Some enzymes are proposed as markers of resilience, among which glyoxalase I, glutathione reductase, thioredoxin reductase, and cinnamyl alcohol dehydrogenase are candidates.PMID:38397397 | DOI:10.3390/biom14020160

Genes (Basel). 2024 Jan 30;15(2):189. doi: 10.3390/genes15020189.ABSTRACTHigh temperature around flowering has a serious impact on the growth and development of maize. However, few maize genes related to flowering under heat stress have been confirmed, and the regulatory mechanism is unclear. To reveal the molecular mechanism of heat tolerance in maize, two maize hybrids, ZD309 and XY335, with different heat resistance, were selected to perform transcriptome and metabolomics analysis at the flowering stage under heat stress. In ZD309, 314 up-regulated and 463 down-regulated differentially expressed genes (DEGs) were detected, while 168 up-regulated and 119 down-regulated DEGs were identified in XY335. By comparing the differential gene expression patterns of ZD309 and XY335, we found the "frontloaded" genes which were less up-regulated in heat-tolerant maize during high temperature stress. They included heat tolerance genes, which may react faster at the protein level to provide resilience to instantaneous heat stress. A total of 1062 metabolites were identified via metabolomics analysis. Lipids, saccharides, and flavonoids were found to be differentially expressed under heat stress, indicating these metabolites' response to high temperature. Our study will contribute to the identification of heat tolerance genes in maize, therefore contributing to the breeding of heat-tolerant maize varieties.PMID:38397179 | DOI:10.3390/genes15020189

Int J Mol Sci. 2024 Feb 19;25(4):2443. doi: 10.3390/ijms25042443.ABSTRACTDepression is twice as prevalent in women as in men, however, most preclinical studies of depression have used male rodent models. This study aimed to examine how stress affects metabolic profiles depending on sex using a rodent depression model: sub-chronic variable stress (SCVS). The SCVS model of male and female mice was established in discovery and validation sets. The stress-induced behavioral phenotypic changes were similar in both sexes, however, the metabolic profiles of female plasma and brain became substantially different after stress, whereas those of males did not. Four stress-differential plasma metabolites-β-hydroxybutyric acid (BHB), L-serine, glycerol, and myo-inositol-could yield biomarker panels with excellent performance to discern the stressed individuals only for females. Disturbances in BHB, glucose, 1,5-anhydrosorbitol, lactic acid, and several fatty acids in the plasma of stressed females implied a systemic metabolic shift to β-oxidation in females. The plasma levels of BHB and corticosterone only in stressed females were observed not only in SCVS but also in an acute stress model. These results collectively suggest a sex difference in the metabolic responses by stress, possibly involving the energy metabolism shift to β-oxidation and the HPA axis dysregulation in females.PMID:38397124 | DOI:10.3390/ijms25042443

Int J Mol Sci. 2024 Feb 19;25(4):2441. doi: 10.3390/ijms25042441.ABSTRACTChronic and excessive ultraviolet (UVA/UVB) irradiation exposure is known as a major contributor to premature skin aging, which leads to excessive reactive oxygen species generation, disturbed extracellular matrix homeostasis, DNA damage, and chronic inflammation. Sunscreen products are the major preventive option against UVR-induced photodamage, mostly counteracting the acute skin effects and only mildly counteracting accelerated aging. Therefore, novel anti-photoaging and photopreventive compounds are a subject of increased scientific interest. Our previous investigations revealed that the endemic plant Haberlea rhodopensis Friv. (HRE) activates the antioxidant defense through an NRF2-mediated mechanism in neutrophiles. In the present study, we aimed to investigate the photoprotective potential of HRE and two of its specialized compounds-the phenylethanoid glycosides myconoside (MYC) and calceolarioside E (CAL)-in UVA/UVB-stimulated human keratinocytes in an in vitro model of photoaging. The obtained data demonstrated that the application of HRE, MYC, and CAL significantly reduced intracellular ROS formation in UVR-exposed HaCaT cells. The NRF2/PGC-1α and TGF-1β/Smad/Wnt signaling pathways were pointed out as having a critical role in the observed CAL- and MYC-induced photoprotective effect. Collectively, CAL is worth further evaluation as a potent natural NRF2 activator and a promising photoprotective agent that leads to the prevention of UVA/UVB-induced premature skin aging.PMID:38397118 | DOI:10.3390/ijms25042441

Int J Mol Sci. 2024 Feb 18;25(4):2407. doi: 10.3390/ijms25042407.ABSTRACTThe complexity of macrophage (MΦ) plasticity and polarization states, which include classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) MΦ phenotypes, is becoming increasingly appreciated. Within the M2 MΦ polarization state, M2a, M2b, M2c, and M2d MΦ subcategories have been defined based on their expression of specific cell surface receptors, secreted cytokines, and specialized immune effector functions. The importance of immunometabolic networks in mediating the function and regulation of MΦ immune responses is also being increasingly recognized, although the exact mechanisms and extent of metabolic modulation of MΦ subtype phenotypes and functions remain incompletely understood. In this study, proton (1H) nuclear magnetic resonance (NMR) metabolomics was employed to determine the polar metabolomes of M2 MΦ subtypes and to investigate the relationship between aqueous metabolite profiles and M2 MΦ functional phenotypes. Results from this study demonstrate that M2a MΦs are most distinct from M2b, M2c, and M2d MΦ subtypes, and that M2b MΦs display several metabolic traits associated with an M1-like MΦ phenotype. The significance of metabolome differences for metabolites implicated in glycolysis, the tricarboxylic acid (TCA) cycle, phospholipid metabolism, and creatine-phosphocreatine cycling is discussed. Altogether, this study provides biochemical insights into the role of metabolism in mediating the specialized effector functions of distinct M2 MΦ subtypes and supports the concept of a continuum of macrophage activation states rather than two well-separated and functionally distinct M1/M2 MΦ classes, as originally proposed within a classical M1/M2 MΦ framework.PMID:38397084 | DOI:10.3390/ijms25042407

Int J Mol Sci. 2024 Feb 17;25(4):2381. doi: 10.3390/ijms25042381.ABSTRACTColorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013-2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient's response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs.PMID:38397058 | DOI:10.3390/ijms25042381

Int J Mol Sci. 2024 Feb 15;25(4):2294. doi: 10.3390/ijms25042294.ABSTRACTGiven its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients' self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.PMID:38396971 | DOI:10.3390/ijms25042294

Int J Mol Sci. 2024 Feb 13;25(4):2247. doi: 10.3390/ijms25042247.ABSTRACTDiabetes is recognized as a risk factor for cognitive decline, but the underlying mechanisms remain elusive. We aimed to identify the metabolic pathways altered in diabetes-associated cognitive decline (DACD) using untargeted metabolomics. We conducted liquid chromatography-mass spectrometry-based untargeted metabolomics to profile serum metabolite levels in 100 patients with type 2 diabetes (T2D) (54 without and 46 with DACD). Multivariate statistical tools were used to identify the differentially expressed metabolites (DEMs), and enrichment and pathways analyses were used to identify the signaling pathways associated with the DEMs. The receiver operating characteristic (ROC) analysis was employed to assess the diagnostic accuracy of a set of metabolites. We identified twenty DEMs, seven up- and thirteen downregulated in the DACD vs. DM group. Chemometric analysis revealed distinct clustering between the two groups. Metabolite set enrichment analysis found significant enrichment in various metabolite sets, including galactose metabolism, arginine and unsaturated fatty acid biosynthesis, citrate cycle, fructose and mannose, alanine, aspartate, and glutamate metabolism. Pathway analysis identified six significantly altered pathways, including arginine and unsaturated fatty acid biosynthesis, and the metabolism of the citrate cycle, alanine, aspartate, glutamate, a-linolenic acid, and glycerophospholipids. Classifier models with AUC-ROC > 90% were developed using individual metabolites or a combination of individual metabolites and metabolite ratios. Our study provides evidence of perturbations in multiple metabolic pathways in patients with DACD. The distinct DEMs identified in this study hold promise as diagnostic biomarkers for DACD patients.PMID:38396924 | DOI:10.3390/ijms25042247

Int J Mol Sci. 2024 Feb 11;25(4):2187. doi: 10.3390/ijms25042187.ABSTRACTDrought stress is a major abiotic factor affecting tomato production and fruit quality. However, the genes and metabolites associated with tomato responses to water deficiency and rehydration are poorly characterized. To identify the functional genes and key metabolic pathways underlying tomato responses to drought stress and recovery, drought-susceptible and drought-tolerant inbred lines underwent transcriptomic and metabolomic analyses. A total of 332 drought-responsive and 491 rehydration-responsive core genes were robustly differentially expressed in both genotypes. The drought-responsive and rehydration-responsive genes were mainly related to photosynthesis-antenna proteins, nitrogen metabolism, plant-pathogen interactions, and the MAPK signaling pathway. Various transcription factors, including homeobox-leucine zipper protein ATHB-12, NAC transcription factor 29, and heat stress transcription factor A-6b-like, may be vital for tomato responses to water status. Moreover, 24,30-dihydroxy-12(13)-enolupinol, caffeoyl hawthorn acid, adenosine 5'-monophosphate, and guanosine were the key metabolites identified in both genotypes under drought and recovery conditions. The combined transcriptomic and metabolomic analysis highlighted the importance of 38 genes involved in metabolic pathways, the biosynthesis of secondary metabolites, the biosynthesis of amino acids, and ABC transporters for tomato responses to water stress. Our results provide valuable clues regarding the molecular basis of drought tolerance and rehydration. The data presented herein may be relevant for genetically improving tomatoes to enhance drought tolerance.PMID:38396864 | DOI:10.3390/ijms25042187

Int J Mol Sci. 2024 Feb 10;25(4):2141. doi: 10.3390/ijms25042141.ABSTRACTAspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE had excellent thromboprophylaxis and inhibition of platelet aggregation. This study aimed to investigate the effect of AEE on the liver of thrombosed rats to reveal its mechanism of thromboprophylaxis. Therefore, a multi-omics approach was used to analyze the liver. Transcriptome results showed 132 differentially expressed genes (DEGs) in the AEE group compared to the model group. Proteome results showed that 159 differentially expressed proteins (DEPs) were identified in the AEE group compared to the model group. Six proteins including fibrinogen alpha chain (Fga), fibrinogen gamma chain (Fgg), fibrinogen beta chain (Fgb), orosomucoid 1 (Orm1), hemopexin (Hpx), and kininogen-2 (Kng2) were selected for parallel reaction monitoring (PRM) analysis. The results showed that the expression of all six proteins was upregulated in the model group compared with the control group. In turn, AEE reversed the upregulation trend of these proteins to some degree. Metabolome results showed that 17 metabolites were upregulated and 38 were downregulated in the model group compared to the control group. AEE could reverse the expression of these metabolites to some degree and make them back to normal levels. The metabolites were mainly involved in metabolic pathways, including linoleic acid metabolism, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. Comprehensive analyses showed that AEE could prevent thrombosis by inhibiting platelet activation, decreasing inflammation, and regulating amino acid and energy metabolism. In conclusion, AEE can have a positive effect on thrombosis-related diseases.PMID:38396823 | DOI:10.3390/ijms25042141