PubMed

Int J Mol Sci. 2023 Dec 12;24(24):17379. doi: 10.3390/ijms242417379.ABSTRACTThe endocannabinoid system regulates physiological processes, and the modulation of endogenous endocannabinoid (eCB) levels is an attractive tool to contrast the development of pathological skin conditions including cancers. Inhibiting FAAH (fatty acid amide hydrolase), the degradation enzyme of the endocannabinoid anandamide (AEA) leads to the increase in AEA levels, thus enhancing its biological effects. Here, we evaluated the anticancer property of the FAAH inhibitor URB597, investigating its potential to counteract epithelial-to-mesenchymal transition (EMT), a process crucially involved in tumor progression. The effects of the compound were determined in primary human keratinocytes, ex vivo skin explants, and the squamous carcinoma cell line A431. Our results demonstrate that URB597 is able to hinder the EMT process by downregulating mesenchymal markers and reducing migratory potential. These effects are associated with the dampening of the AKT/STAT3 signal pathways and reduced release of pro-inflammatory cytokines and tumorigenic lipid species. The ability of URB597 to contrast the EMT process provides insight into effective approaches that may also include the use of FAAH inhibitors for the treatment of skin cancers.PMID:38139209 | DOI:10.3390/ijms242417379

Int J Mol Sci. 2023 Dec 11;24(24):17366. doi: 10.3390/ijms242417366.ABSTRACTβ-Farnesene is an advanced molecule with promising applications in agriculture, the cosmetics industry, pharmaceuticals, and bioenergy. To supplement the shortcomings of rational design in the development of high-producing β-farnesene strains, a Metabolic Pathway Design-Fermentation Test-Metabolomic Analysis-Target Mining experimental cycle was designed. In this study, by over-adding 20 different amino acids/nucleobases to induce fluctuations in the production of β-farnesene, the changes in intracellular metabolites in the β-farnesene titer-increased group were analyzed using non-targeted metabolomics. Differential metabolites that were detected in each experimental group were selected, and their metabolic pathways were located. Based on these differential metabolites, targeted strain gene editing and culture medium optimization were performed. The overexpression of the coenzyme A synthesis-related gene pantothenate kinase (PanK) and the addition of four mixed water-soluble vitamins in the culture medium increased the β-farnesene titer in the shake flask to 1054.8 mg/L, a 48.5% increase from the initial strain. In the subsequent fed-batch fermentation, the β-farnesene titer further reached 24.6 g/L. This work demonstrates the tremendous application value of metabolomics analysis for the development of industrial recombinant strains and the optimization of fermentation conditions.PMID:38139198 | DOI:10.3390/ijms242417366

Int J Mol Sci. 2023 Dec 11;24(24):17359. doi: 10.3390/ijms242417359.ABSTRACTLate spring cold is a disastrous weather condition that often affects early rice seedlings in southern China, limiting the promotion of direct seeding cultivation. However, there are few reports on the effect of these events and on the growth recovery mechanism of rice root systems after rice seedlings are exposed to this stress. This study selected the strong-growth-recovery variety B116 (R310/R974, F17) and the slow-recovery variety B811 (Zhonghui 286) for direct seeding cultivation and exposed them to low temperature and low-light stress to simulate a late spring cold event in an artificial climate chamber. The treatment consisted of 4 days of exposure to a day/night temperature of 14/10 °C and a light intensity of 266 µmol m-2s-1 while the control group was kept at a day/night temperature of 27/25 °C and light intensity of 533 µmol m-2s-1. The results showed that 6 days after stress, the total length, surface area, and volume of B116 roots increased by 335.5%, 290.1%, and 298.5%, respectively, while those of B811 increased by 228.8%, 262.0%, and 289.1%, respectively. In B116, the increase in root fresh weight was 223.1%, and that in B811 was 165.6%, demonstrating rapid root recovery after stress and significant differences among genotypes. The content of H2O2 and MDA in the B116 roots decreased faster than that in the B811 roots after normal light intensity and temperature conditions were restored, and the activity of ROS metabolism enzymes was stronger in B116 roots than in B811 roots. The correlation analysis between the transcriptome and metabolome showed that endogenous signal transduction and starch and sucrose metabolism were the main metabolic pathways affecting the rapid growth of rice seedling roots after exposure to combined stress from low temperature and low light intensities. The levels of auxin and sucrose in the roots of the strong-recovery variety B116 were higher, and this variety's metabolism was downregulated significantly faster than that of B811. The auxin response factor and sucrose synthesis-related genes SPS1 and SUS4 were significantly upregulated. This study contributes to an understanding of the rapid growth recovery mechanism in rice after exposure to combined stress from low-temperature and low-light conditions.PMID:38139187 | DOI:10.3390/ijms242417359

Int J Mol Sci. 2023 Dec 9;24(24):17302. doi: 10.3390/ijms242417302.ABSTRACTThe study of an organism's response to cerebral ischemia at different levels is essential to understanding the mechanism of the injury and protection. A great interest is devoted to finding the links between quantitative metabolic changes and post-ischemic damage. This work aims to summarize the outcomes of the most studied metabolites in brain tissue-lactate, glutamine, GABA (4-aminobutyric acid), glutamate, and NAA (N-acetyl aspartate)-regarding their biological function in physiological conditions and their role after cerebral ischemia/reperfusion. We focused on ischemic damage and post-ischemic recovery in both experimental-including our results-as well as clinical studies. We discuss the role of blood glucose in view of the diverse impact of hyperglycemia, whether experimentally induced, caused by insulin resistance, or developed as a stress response to the cerebral ischemic event. Additionally, based on our and other studies, we analyze and critically discuss post-ischemic alterations in energy metabolites and the elevation of blood ketone bodies observed in the studies on rodents. To complete the schema, we discuss alterations in blood plasma circulating amino acids after cerebral ischemia. So far, no fundamental brain or blood metabolite(s) has been recognized as a relevant biological marker with the feasibility to determine the post-ischemic outcome or extent of ischemic damage. However, studies from our group on rats subjected to protective ischemic preconditioning showed that these animals did not develop post-ischemic hyperglycemia and manifested a decreased metabolic infringement and faster metabolomic recovery. The metabolomic approach is an additional tool for understanding damaging and/or restorative processes within the affected brain region reflected in the blood to uncover the response of the whole organism via interorgan metabolic communications to the stressful cerebral ischemic challenge.PMID:38139131 | DOI:10.3390/ijms242417302

Int J Mol Sci. 2023 Dec 7;24(24):17211. doi: 10.3390/ijms242417211.ABSTRACTType 2 diabetes is a non-communicable metabolic syndrome that is characterized by the dysfunction of pancreatic β-cells and insulin resistance. Both animal and human studies have been conducted, demonstrating that helminth infections are associated with a decreased prevalence of type 2 diabetes mellitus (T2DM). However, there is a paucity of information on the impact that helminths have on the metabolome of the host and how the infection ameliorates T2DM or its progression. Therefore, this study aimed at using a non-targeted metabolomics approach to systematically identify differentiating metabolites from serum samples of T2DM-induced Sprague Dawley (SD) rats infected with a tissue-dwelling nematode, Trichinella zimbabwensis, and determine the metabolic pathways impacted during comorbidity. Forty-five male SD rats with a body weight between 160 g and 180 g were used, and these were randomly selected into control (non-diabetic and not infected with T. zimbabwensis) (n = 15) and T2DM rats infected with T. zimbabwensis (TzDM) (n = 30). The results showed metabolic separation between the two groups, where d-mannitol, d-fructose, and glucose were upregulated in the TzDM group, when compared to the control group. L-tyrosine, glycine, diglycerol, L-lysine, and L-hydroxyproline were downregulated in the TzDM group when compared to the control group. Metabolic pathways which were highly impacted in the TzDM group include biotin metabolism, carnitine synthesis, and lactose degradation. We conclude from our study that infecting T2DM rats with a tissue-dwelling nematode, T. zimbabwensis, causes a shift in the metabolome, causing changes in different metabolic pathways. Additionally, the infection showed the potential to regulate or improve diabetes complications by causing a decrease in the amino acid concentration that results in metabolic syndrome.PMID:38139040 | DOI:10.3390/ijms242417211

Int J Mol Sci. 2023 Dec 6;24(24):17175. doi: 10.3390/ijms242417175.ABSTRACTThe ex vivo treatment of a limited volume of blood with gaseous oxygen-ozone (O2-O3) mixtures and its rapid reinfusion into the patient is a widespread medical procedure. O3 instantly reacts with the blood's antioxidant systems, disappearing before reinfusion, although the molecules formed act as messengers in the organism, inducing multiple antioxidant and anti-inflammatory responses. An appropriate dose of O3 is obviously essential to ensure both safety and therapeutic efficacy, and in recent years, the low-dose O3 concept has led to a significant reduction in the administered O3 concentrations. However, the molecular events triggered by such low concentrations in the blood still need to be fully elucidated. In this basic study, we analysed the molecular modifications induced ex vivo in sheep blood by 5 and 10 µg O3/mL O2 by means of a powerful metabolomics analysis in association with haemogas, light microscopy and bioanalytical assays. This combined approach revealed increased oxygenation and an increased antioxidant capacity in the O3-treated blood, which accorded with the literature. Moreover, original information was obtained on the impact of these low O3 concentrations on the metabolic pathways of amino acids, carbohydrates, lipids and nucleotides, with the modified metabolites being mostly involved in the preservation of the oxidant-antioxidant balance and in energy production.PMID:38139004 | DOI:10.3390/ijms242417175

Int J Mol Sci. 2023 Dec 5;24(24):17148. doi: 10.3390/ijms242417148.ABSTRACTDendrobium Sw. (family Orchidaceae) is a renowned edible and medicinal plant in China. Although widely cultivated and used, less research has been conducted on differential Dendrobium species. In this study, stems from seven distinct Dendrobium species were subjected to UPLC-QTOF-MS/MS analysis. A total of 242 metabolites were annotated, and multivariate statistical analysis was employed to explore the variance in the extracted metabolites across the various groups. The analysis demonstrated that D. nobile displays conspicuous differences from other species of Dendrobium. Specifically, D. nobile stands out from the remaining six taxa of Dendrobium based on 170 distinct metabolites, mainly terpene and flavonoid components, associated with cysteine and methionine metabolism, flavonoid biosynthesis, and galactose metabolism. It is believed that the variations between D. nobile and other Dendrobium species are mainly attributed to three metabolite synthesis pathways. By comparing the chemical composition of seven species of Dendrobium, this study identified the qualitative components of each species. D. nobile was found to differ significantly from other species, with higher levels of terpenoids, flavonoids, and other compounds that are for the cardiovascular field. By comparing the chemical composition of seven species of Dendrobium, these qualitative components have relevance for establishing quality standards for Dendrobium.PMID:38138977 | DOI:10.3390/ijms242417148

Int J Mol Sci. 2023 Dec 5;24(24):17133. doi: 10.3390/ijms242417133.ABSTRACTExogenous ethylene is commonly utilized to initiate flower induction in pineapple (Ananas comosus (L.) Merr.). However, the molecular mechanisms and metabolic changes involved are not well understood. In this study, we explored the genetic network and metabolic shifts in the 'Comte de Paris' pineapple variety during ethylene-induced flowering. This was achieved through an integrative analysis of metabolome and transcriptome profiles at vegetative shoot apexes (0 d after ethephon treatment named BL_0d), the stage of bract primordia (8 d after ethephon treatment named BL_8d), stage of flower primordia (18 d after ethephon treatment named BL_18d), and the stage of stopped floret differentiation (34 d after ethephon treatment named BL_34d). We isolated and identified 804 metabolites in the pineapple shoot apex and inflorescence, categorized into 24 classes. Notably, 29, 31, and 46 metabolites showed significant changes from BL_0d to BL_8d, BL_8d to BL_18d, and BL_18d to BL_34d, respectively. A marked decrease in indole was observed, suggesting its role as a characteristic metabolite during flower induction. Transcriptomic analysis revealed 956, 1768, and 4483 differentially expressed genes (DEGs) for BL_0d vs. BL_8d, BL_8d vs. BL_18d, and BL_18d vs. BL_34d, respectively. These DEGs were significantly enriched in carbohydrate metabolism and hormone signaling pathways, indicating their potential involvement in flower induction. Integrating metabolomic and transcriptomic data, we identified several candidate genes, such as Agamous-Like9 (AGL9), Ethylene Insensitive 3-like (ETIL3), Apetala2 (AP2), AP2-like ethylene-responsive transcription factor ANT (ANT), and Sucrose synthase 2 (SS2), that play potentially crucial roles in ethylene-induced flower induction in pineapple. We also established a regulatory network for pineapple flower induction, correlating metabolites and DEGs, based on the Arabidopsis thaliana pathway as a reference. Overall, our findings offer a deeper understanding of the metabolomic and molecular mechanisms driving pineapple flowering.PMID:38138962 | DOI:10.3390/ijms242417133

Molecules. 2023 Dec 14;28(24):8088. doi: 10.3390/molecules28248088.ABSTRACTAs a beneficial nutrient and essential trace element, selenium plays a significant role in plant growth functions and human protein biosynthesis. Plant selenium enrichment is mainly obtained from both natural soil and exogenous selenium supplementation, while human beings consume selenium-enriched foods for the purposes of selenium supplementation. In this study, different types of selenium fertilizers were sprayed onto Lycium barbarum in Ningxia, and transcriptomics and metabolomics techniques were used to explore the effects of selenium on the fruit differentials and differential genes in Lycium barbarum. Taking the "Ning Qiyi No.1" wolfberry as the research object, sodium selenite, nano-selenium, and organic selenium were sprayed at a concentration of 100 mg·L-1 three times from the first fruiting period to the harvesting period, with a control treatment comprising the spraying of clear water. We determined the major metabolites and differential genes of the amino acids and derivatives, flavonoids, and alkaloids in ripe wolfberries. We found that spraying selenium significantly enhanced the Lycium barbarum metabolic differentiators; the most effective spray was the organic selenium, with 129 major metabolic differentiators and 10 common metabolic pathways screened after spraying. Nano-selenium was the next best fertilizer we screened, with 111 major metabolic differentiators, the same number as organic selenium in terms of differential genes and common metabolite pathways. Sodium selenite was the least effective of the three, with only 59 of its major metabolic differentials screened, but its differential genes and metabolites were enriched for five common pathways.PMID:38138577 | DOI:10.3390/molecules28248088

Molecules. 2023 Dec 5;28(24):7944. doi: 10.3390/molecules28247944.ABSTRACTArmillaria mellea (Vahl) P. Kumm is commonly used for food and pharmaceutical supplements due to its immune regulatory function, and polysaccharides are one of its main components. The aim of this research is to study the immunological activity of the purified acidic polysaccharide fraction, namely, AMPA, isolated from Armillaria mellea crude polysaccharide (AMP). In this study, a combination of the immune activity of mouse macrophages in vitro and serum metabonomics in vivo was used to comprehensively explore the cell viability and metabolic changes in immune-deficient mice in the AMPA intervention, with the aim of elucidating the potential mechanisms of AMPA in the treatment of immunodeficiency. The in vitro experiments revealed that, compared with LPS-induced RAW264.7, the AMPA treatment elevated the levels of the cellular immune factors IL-2, IL-6, IgM, IgA, TNF-α, and IFN-γ; promoted the expression of immune proteins; and activated the TLR4/MyD88/NF-κB signaling pathway to produce immunological responses. The protein expression was also demonstrated in the spleen of the cyclophosphamide immunosuppressive model in vivo. The UHPLC-MS-based metabolomic analysis revealed that AMPA significantly modulated six endogenous metabolites in mice, with the associated metabolic pathways of AMPA for treating immunodeficiency selected as potential therapeutic biomarkers. The results demonstrate that phosphorylated acetyl CoA, glycolysis, and the TCA cycle were mainly activated to enhance immune factor expression and provide immune protection to the body. These experimental results are important for the development and application of AMPA as a valuable health food or drug that enhances immunity.PMID:38138434 | DOI:10.3390/molecules28247944

Microorganisms. 2023 Dec 10;11(12):2954. doi: 10.3390/microorganisms11122954.ABSTRACTApplying plant-derived fungicides is a safe and sustainable way to control wheat scab. In this study, volatile organic compounds (VOCs) of wheat cultivars with and without the resistance gene Fhb1 were analyzed by GC-MS, and 2-phenylethanol was screened out. The biocontrol function of 2-phenylethanol on Fusarium graminearum was evaluated in vitro and in vivo. Metabolomics analysis indicated that 2-phenylethanol altered the amino acid pathways of F. graminearum, affecting its normal life activities. Under SEM and TEM observation, the mycelial morphology changed, and the integrity of the cell membrane was destroyed. Furthermore, 2-phenylethanol could inhibit the production of mycotoxins (DON, 3-ADON, 15-ADON) by F. graminearum and reduce grain contamination. This research provides new ideas for green prevention and control of wheat FHB in the field.PMID:38138097 | DOI:10.3390/microorganisms11122954

Microorganisms. 2023 Nov 22;11(12):2831. doi: 10.3390/microorganisms11122831.ABSTRACTCandida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen's strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans' life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection.PMID:38137975 | DOI:10.3390/microorganisms11122831

Life (Basel). 2023 Dec 15;13(12):2343. doi: 10.3390/life13122343.ABSTRACTOsteoarthritis (OA) is a degenerative joint condition with limited disease-modifying treatments currently. Palm tocotrienol-rich fraction (TRF) has been previously shown to be effective against OA, but its mechanism of action remains elusive. This study aims to compare serum metabolomic alteration in Sprague-Dawley rats with monosodium iodoacetate (MIA)-induced OA which were treated with palm TRF, glucosamine sulphate, or a combination of both. This study was performed on thirty adult male rats, which were divided into normal control (n = 6) and OA groups (n = 24). The OA group received intra-articular injections of MIA and daily oral treatments of refined olive oil (vehicle, n = 6), palm TRF (100 mg/kg, n = 6), glucosamine sulphate (250 mg/kg, n = 6), or a combination of TRF and glucosamine (n = 6) for four weeks. Serum was collected at the study's conclusion for metabolomic analysis. The findings revealed that MIA-induced OA influences amino acid metabolism, leading to changes in metabolites associated with the biosynthesis of phenylalanine, tyrosine and tryptophan as well as alterations in the metabolism of phenylalanine, tryptophan, arginine and proline. Supplementation with glucosamine sulphate, TRF, or both effectively reversed these metabolic changes induced by OA. The amelioration of metabolic effects induced by OA is linked to the therapeutic effects of TRF and glucosamine. However, it remains unclear whether these effects are direct or indirect in nature.PMID:38137944 | DOI:10.3390/life13122343

Life (Basel). 2023 Dec 13;13(12):2335. doi: 10.3390/life13122335.ABSTRACTMaintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they constitute a major biomass in oceans, being an important food source for fish and functioning in the carbon cycle. The potential impact of climate change on copepod populations is an area of intense study. Omics technologies offer the potential to detect early metabolic alterations induced by the stresses of climate change. One such omics approach is lipidomics, which can accurately quantify changes in lipid pools serving structural, signal transduction, and energy roles. We utilized high-resolution mass spectrometry (≤2 ppm mass error) to characterize the lipidome of three different species of copepods in an effort to identify lipid-based biomarkers of copepod health and viability which are more sensitive than observational tools. With the establishment of such a lipid database, we will have an analytical platform useful for prospectively monitoring the lipidome of copepods in a planned long-term five-year ecological study of climate change on this oceanic sentinel species. The copepods examined in this pilot study included a North Atlantic species (Calanus finmarchicus) and two species from the Gulf of Mexico, one a filter feeder (Acartia tonsa) and one a hunter (Labidocerca aestiva). Our findings clearly indicate that the lipidomes of copepod species can vary greatly, supporting the need to obtain a broad snapshot of each unique lipidome in a long-term multigeneration prospective study of climate change. This is critical, since there may well be species-specific responses to the stressors of climate change and co-stressors such as pollution. While lipid nomenclature and biochemistry are extremely complex, it is not essential for all readers interested in climate change to understand all of the various lipid classes presented in this study. The clear message from this research is that we can monitor key copepod lipid families with high accuracy, and therefore potentially monitor lipid families that respond to environmental perturbations evoked by climate change.PMID:38137936 | DOI:10.3390/life13122335

J Clin Med. 2023 Dec 8;12(24):7584. doi: 10.3390/jcm12247584.ABSTRACTBACKGROUND: Intestinal diseases are identified as autoimmune phenomena attributed to a specific virus that binds to the mucosal epithelium. The importance of precise diagnostic processes and identification is emphasized, but the multifaceted and complex etiological factors pose challenges for effective treatment. A recent supplementary study suggested a linkage between the secretion of calprotectin, a protein associated with inflammatory processes, and increased levels of hydroxyeicosatrienoic acids (HETE) and hydroxyoctadecadienoic (HODE) compounds.METHODS: Sixty-two patients (average age: 14.06 ± 2.93 years) suffering from inflammatory bowel diseases were included in this study. Comparative analyses were performed to assess the concentrations of calprotectin against the levels of arachidonic acid derivatives. The calprotectin concentration was determined using the enzyme-linked immunosorbent assay (ELISA) method. The derivatives of HETE and HODE were identified through liquid chromatography.RESULTS: Patients with Crohn's disease (CD) displayed higher average concentrations of fatty acid metabolites; however, no correlation with calprotectin was observed. A dependency of 12S HETE concentration relative to age was noted in the CD group, and a similar trend was also identified in ulcerative colitis (UC), with the significant metabolites being 15 HETE and 5 oxoETE. In UC patients, a positive correlation was established between the calprotectin concentration and the acids 5-HETE and 12-HETE.CONCLUSIONS: These findings may be instrumental for monitoring the inflammatory states of patients and indicating a pathway for intervention. The metabolite 16RS HETE is associated with UC activity, and 15-HETE is related to the disease's duration. A relatively more significant role of HETE acids in the progression of the disease was observed in UC.PMID:38137653 | DOI:10.3390/jcm12247584

Biomedicines. 2023 Dec 13;11(12):3303. doi: 10.3390/biomedicines11123303.ABSTRACTThe objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with the CON, the HFF diet increased the total cholic acid (CA) and the CA to chenodeoxycholic acid (CDCA) ratio in the liver, DI, and blood. CA and CDCA levels in the DI were negatively and positively correlated with ileal FGF19 expression, respectively, and blood levels of FGF19 decreased with an increasing ileal CA to CDCA ratio. Compared with the CON, the HFF diet increased the gene expression of hepatic 12-alpha-hydrolase, which catalyzes the synthesis of CA in the liver. Since CA species are weaker FXR ligands than CDCA, our results suggest that impairment of FXR-FGF19 signaling in NAFLD pigs is associated with a decrease in FXR agonism in the bile acid pool.PMID:38137523 | DOI:10.3390/biomedicines11123303

Biomedicines. 2023 Dec 13;11(12):3295. doi: 10.3390/biomedicines11123295.ABSTRACTAntipsychotics are an important pharmacotherapy option for the treatment of many mental illnesses. Unfortunately, selecting antipsychotics is often a trial-and-error process due to a lack of understanding as to which medications an individual patient will find most effective and best tolerated. Metabolomics, or the study of small molecules in a biosample, is an increasingly used omics platform that has the potential to identify biomarkers for medication efficacy and toxicity. This systematic review was conducted to identify metabolites and metabolomic pathways associated with antipsychotic use in humans. Ultimately, 42 studies were identified for inclusion in this review, with all but three studies being performed in blood sources such as plasma or serum. A total of 14 metabolite classes and 12 lipid classes were assessed across studies. Although the studies were highly heterogeneous in approach and mixed in their findings, increases in phosphatidylcholines, decreases in carboxylic acids, and decreases in acylcarnitines were most consistently noted as perturbed in patients exposed to antipsychotics. Furthermore, for the targeted metabolomic and lipidomic studies, seven metabolites and three lipid species had findings that were replicated. The most consistent finding for targeted studies was an identification of a decrease in aspartate with antipsychotic treatment. Studies varied in depth of detail provided for their study participants and in study design. For example, in some cases, there was a lack of detail on specific antipsychotics used or concomitant medications, and the depth of detail on sample handling and analysis varied widely. The conclusions here demonstrate that there is a large foundation of metabolomic work with antipsychotics that requires more complete reporting so that an objective synthesis such as a meta-analysis can take place. This will then allow for validation and clinical application of the most robust findings to move the field forward. Future studies should be carefully controlled to take advantage of the sensitivity of metabolomics while limiting potential confounders that may result from participant heterogeneity and varied analysis approaches.PMID:38137517 | DOI:10.3390/biomedicines11123295

Biomedicines. 2023 Dec 1;11(12):3201. doi: 10.3390/biomedicines11123201.ABSTRACTAptamers, short strands of either DNA, RNA, or peptides, known for their exceptional specificity and high binding affinity to target molecules, are providing significant advancements in the field of health. When seamlessly integrated into biosensor platforms, aptamers give rise to aptasensors, unlocking a new dimension in point-of-care diagnostics with rapid response times and remarkable versatility. As such, this review aims to present an overview of the distinct advantages conferred by aptamers over traditional antibodies as the molecular recognition element in biosensors. Additionally, it delves into the realm of specific aptamers made for the detection of biomarkers associated with infectious diseases, cancer, cardiovascular diseases, and metabolomic and neurological disorders. The review further elucidates the varying binding assays and transducer techniques that support the development of aptasensors. Ultimately, this review discusses the current state of point-of-care diagnostics facilitated by aptasensors and underscores the immense potential of these technologies in advancing the landscape of healthcare delivery.PMID:38137422 | DOI:10.3390/biomedicines11123201

Foods. 2023 Dec 15;12(24):4493. doi: 10.3390/foods12244493.ABSTRACTSea buckthorn (Hippophae rhamnoides L.) (SB) is increasingly consumed worldwide as a food and food supplement. The remarkable richness in biologically active phytochemicals (polyphenols, carotenoids, sterols, vitamins) is responsible for its purported nutritional and health-promoting effects. Despite the considerable interest and high market demand for SB-based supplements, a limited number of studies report on the authentication of such commercially available products. Herein, untargeted metabolomics based on ultra-high-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UHPLC-QTOF-ESI+MS) were able to compare the phytochemical fingerprint of leaves, berries, and various categories of SB-berry herbal supplements (teas, capsules, tablets, liquids). By untargeted metabolomics, a multivariate discrimination analysis and a univariate approach (t-test and ANOVA) showed some putative authentication biomarkers for berries, e.g., xylitol, violaxanthin, tryptophan, quinic acid, quercetin-3-rutinoside. Significant dominant molecules were found for leaves: luteolin-5-glucoside, arginine, isorhamnetin 3-rutinoside, serotonin, and tocopherol. The univariate analysis showed discriminations between the different classes of food supplements using similar algorithms. Finally, eight molecules were selected and considered significant putative authentication biomarkers. Further studies will be focused on quantitative evaluation.PMID:38137297 | DOI:10.3390/foods12244493

Foods. 2023 Dec 14;12(24):4486. doi: 10.3390/foods12244486.ABSTRACTChina Xihu Longjing tea is famous for its good flavor and quality. However, information on its related metabolites, except for flavonoids, is largely deficient. Different processing methods for China Xihu Longjing tea fixing-by machines at both the first and second step (A1), first step by machine and second step by hand (A2), first step by hand and second step by machine (A3), and by hand at both the first and second step (A4)-were compared using a UHPLC-QE-MS-based metabolomics approach. Liquid chromatography-mass spectrometry was used to analyze the metabolic profiles of the processed samples. A total of 490 metabolites (3 alkaloids, 3 anthracenes, 15 benzene and substituted derivatives, 2 benzopyrans, 13 coumarins and derivatives, 128 flavonoids, 4 furanoid lignans, 16 glycosides and derivatives, 5 indoles and derivatives, 18 isocoumarins and derivatives, 4 chalcones and dihydrochalcones, 4 naphthopyrans, 3 nucleosides, 78 organic acids and derivatives, 55 organooxygen compounds, 5 phenols, 109 prenol lipids, 3 saccharolipids, 3 steroids and steroid derivatives, and 17 tannins) were identified. The different metabolic profiles were distinguished using PCA and OPLS-DA. There were differences in the types and contents of the metabolites, especially flavonoids, furanoid lignans, glycosides and derivatives, organic acids and derivatives, and organooxygen compounds. There was a positive correlation between flavonoid metabolism and amino acid metabolism. However, there was a negative correlation between flavonoid metabolism and amino acid metabolism, which had the same trend as prenol lipid metabolism and tannins. This study provides new valuable information regarding differences in the metabolite profile of China Xihu Longjing tea processed based on machine fixing and on manual fixing methods.PMID:38137290 | DOI:10.3390/foods12244486