PubMed

Molecules. 2023 Aug 11;28(16):6009. doi: 10.3390/molecules28166009.ABSTRACTCooking methods affect the compositions of Lentinus edodes metabolites. Nevertheless, little information is available on the specific impact of different cooking methods on Lentinus edodes via metabolomic analysis. This study determined the influence of boiling, steaming, air-frying, and roasting on the metabolomic profiles of Lentinus edodes based on UHPLC-Q-Exactive Orbitrap MS/MS in combination with chemometrics. A total of 990 metabolites were detected and classified into 11 super-classes. Subsequently, the metabolites of the four cooking methods were distinguished using multivariate statistical analysis. The results showed that boiling caused a massive loss of metabolites while roasting and air-frying led to an evident upregulation. The upregulation of metabolites in the steaming groups was not as significant as in roasting and air-frying. This study provided reference data for a comprehensive understanding of the metabolites associated with domestic cooking methods and valuable guidance for the development of Lentinus edodes and its products in the future.PMID:37630261 | DOI:10.3390/molecules28166009

Molecules. 2023 Aug 9;28(16):5974. doi: 10.3390/molecules28165974.ABSTRACTThe rhizome of Atractylodes lancea (Thunb.) DC. (AL), called Maocangzhu in Chinese, is a geoherbalism medical herb in Jiangsu Province that is often used in the prescription of traditional Chinese medicine (TCM), such as for the treatment of COVID-19. The landform and climatic environment of each province varies greatly from south to north, which has an important influence on the chemical constituents in AL. However, there is a lack of research on the significance of its geoherbalism, especially in water-soluble parts other than volatile oil. In this study, eight known compounds were isolated and obtained as reference substances from AL. In addition, liquid chromatography coupled with triple-quadrupole time-of-flight tandem mass spectrometry (LC-triple TOF-MS/MS) and gas chromatography-mass spectrometry (GC-MS) were used to analyze and characterize chemical constituents from different habitats. Moreover, orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to reveal the differential metabolomics in AL from different habitats based on the qualitative information of the chemical constituents. Results showed that a total of 33 constituents from GC-MS and 106 constituents from LC-triple TOF-MS/MS were identified or inferred, including terpenoids, polyacetylenes, and others; meanwhile, the fragmentation pathways of different types of compounds were preliminarily deduced from the fragmentation behavior of the major constituents. According to the variable importance in projection (VIP) and p-values, only one volatile differential metabolite was identified by GC-MS screening: β-eudesmol. Overall, five differential metabolites were identified by LC-triple TOF-MS/MS screening: sucrose, 4(15),11-eudesmadiene; atractylenolide I, 3,5,11-tridecatriene-7,9-diyne-1,2-diacetate, and (3Z,5E,11E)-tridecatriene-7,9-diynyl-1-O-(E)-ferulate. This study provides metabolomic information for the establishment of a comprehensive quality evaluation system for AL.PMID:37630228 | DOI:10.3390/molecules28165974

Molecules. 2023 Aug 9;28(16):5964. doi: 10.3390/molecules28165964.ABSTRACTBeef sausage (BS) is one of the most favored meat products due to its nutrition and good taste. However, for economic purposes, BS is often adulterated with pork by unethical players. Pork consumption is strictly prohibited for religions including Islam and Judaism. Therefore, advanced detection methods are highly required to warrant the halal authenticity of BS. This research aimed to develop a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method to determine the halal authenticity of BS using an untargeted metabolomics approach. LC-HRMS was capable of detecting various metabolites in BS and BS containing pork. The presence of pork in BS could be differentiated using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) with high accuracy. PLS-DA perfectly classified authentic BS and BS containing pork in all concentration levels of pork with R2X = (0.821), R2Y(= 0.984), and Q2 = (0.795). The level of pork in BS was successfully predicted through partial least squares (PLS) and orthogonal PLS (OPLS) chemometrics. Both models gave high R2 (>0.99) actual and predicted values as well as few errors, indicating good accuracy and precision. Identification of discriminating metabolites' potential as biomarker candidates through variable importance for projections (VIP) value revealed metabolites of 2-arachidonyl-sn-glycero-3-phosphoethanolamine, 3-hydroxyoctanoylcarnitine, 8Z,11Z,14Z-eicosatrienoic acid, D-(+)-galactose, oleamide, 3-hydroxyhexadecanoylcarnitine, arachidonic acid, and α-eleostearic acid as good indicators to detect pork. It can be concluded that LC-HRMS metabolomics combined with PCA, PLS-DA, PLS, and OPLS was successfully used to detect pork adulteration in beef sausages. The results imply that LC-HRMS untargeted metabolomics in combination with chemometrics is a promising alternative as an analytical technique to detect pork in sausage products. Further analysis of larger samples is required to warrant the reproducibility.PMID:37630216 | DOI:10.3390/molecules28165964

Molecules. 2023 Aug 9;28(16):5962. doi: 10.3390/molecules28165962.ABSTRACTWine is a temperature, light, and oxygen-sensitive product, so its physicochemical characteristics can be modified by variations in temperature and time when samples are either sampled, transported, and/or analyzed. These changes can alter its metabolomic fingerprinting, impacting further classification tasks and quality/quantitative analyses. For these reasons, the aim of this work is to compare and analyze the information obtained by different chemometric methods used in a complementary form (PCA, ASCA, and PARAFAC) to study 1H-NMR spectra variations of four red wine samples kept at different temperatures and time lapses. In conjunction, distinctive changes in the spectra are satisfactorily tracked with each chemometric method. The chemometric analyses reveal variations related to the wine sample, temperature, and time, as well as the interactions among these factors. Moreover, the magnitude and statistical significance of the effects are satisfactorily accounted for by ASCA, while the time-related effects variations are encountered by PARAFAC modeling. Acetaldehyde, formic acid, polyphenols, carbohydrates, lactic acid, ethyl lactate, methanol, choline, succinic acid, proline, acetoin, acetic acid, 1,3-propanediol, isopentanol, and some amino acids are identified as some of the metabolites which present the most important variations.PMID:37630214 | DOI:10.3390/molecules28165962

Life (Basel). 2023 Aug 4;13(8):1684. doi: 10.3390/life13081684.ABSTRACTBACKGROUND: The major focus of metabolomics research has been confined to the readily available biofluids-urine and blood serum. However, red blood cells (RBCs) are also readily available, and may be a source of a wealth of information on vertebrates. However, the comprehensive metabolomic characterization of RBCs is minimal although they exhibit perturbations in various physiological states. RBCs act as the host of malarial parasites during the symptomatic stage. Thus, understanding the changes in RBC metabolism during infection is crucial for a better understanding of disease progression.METHODS: The metabolome of normal RBCs obtained from Swiss mice was investigated using 1H NMR spectroscopy. Several 1 and 2-dimensional 1H NMR experiments were employed for this purpose. The information from this study was used to investigate the changes in the RBC metabolome during the early stage of infection (~1% infected RBCs) by Plasmodium bergheii ANKA.RESULTS: We identified over 40 metabolites in RBCs. Several of these metabolites were quantitated using 1H NMR spectroscopy. The results indicate changes in the choline/membrane components and other metabolites during the early stage of malaria.CONCLUSIONS: The paper reports the comprehensive characterization of the metabolome of mouse RBCs. Changes during the early stage of malarial infection suggest significant metabolic alteration, even at low parasite content (~1%).GENERAL SIGNIFICANCE: This study should be of use in maximizing the amount of information available from metabolomic experiments on the cellular components of blood. The technique can be directly applied to real-time investigation of infectious diseases that target RBCs.PMID:37629541 | DOI:10.3390/life13081684

Life (Basel). 2023 Jul 25;13(8):1623. doi: 10.3390/life13081623.ABSTRACTFungi are the most diverse living organisms on planet Earth, where their ubiquitous presence in various ecosystems offers vast potential for the research and discovery of new, naturally occurring medicinal products. Concerning human health, cancer remains one of the leading causes of mortality. While extensive research is being conducted on treatments and their efficacy in various stages of cancer, finding cytotoxic drugs that target tumor cells with no/less toxicity toward normal tissue is a significant challenge. In addition, traditional cancer treatments continue to suffer from chemical resistance. Fortunately, the cytotoxic properties of several natural products derived from various microorganisms, including fungi, are now well-established. The current review aims to extract and consolidate the findings of various scientific studies that identified fungi-derived bioactive metabolites with antitumor (anticancer) properties. The antitumor secondary metabolites identified from extremophilic and extremotolerant fungi are grouped according to their biological activity and type. It became evident that the significance of these compounds, with their medicinal properties and their potential application in cancer treatment, is tremendous. Furthermore, the utilization of omics tools, analysis, and genome mining technology to identify the novel metabolites for targeted treatments is discussed. Through this review, we tried to accentuate the invaluable importance of fungi grown in extreme environments and the necessity of innovative research in discovering naturally occurring bioactive compounds for the development of novel cancer treatments.PMID:37629481 | DOI:10.3390/life13081623

Int J Mol Sci. 2023 Aug 19;24(16):12972. doi: 10.3390/ijms241612972.ABSTRACTThe poor response, adverse effects and drug resistance to treatment of acute myeloid leukemia (AML) have led to searching for safer and more effective therapeutic alternatives. We previously demonstrated that the alcoholic extract of Petiveria alliacea (Esperanza) has a significant in vitro antitumor effect on other tumor cells and also the ability to regulate energy metabolism. We evaluated the effect of the Esperanza extract in vitro and in vivo in a murine model of AML with DA-3/ER-GM cells. First, a chemical characterization of the extract was conducted through liquid and gas chromatography coupled with mass spectrometry. In vitro findings showed that the extract modulates tumor metabolism by decreasing glucose uptake and increasing reactive oxygen species, which leads to a reduction in cell proliferation. Then, to evaluate the effect of the extract in vivo, we standardized the mouse model by injecting DA-3/ER-GM cells intravenously. The animals treated with the extract showed a lower percentage of circulating blasts, higher values of hemoglobin, hematocrit, and platelets, less infiltration of blasts in the spleen, and greater production of cytokines compared to the control group. These results suggest that the antitumor activity of this extract on DA-3/ER-GM cells can be attributed to the decrease in glycolytic metabolism, its activity as a mitocan, and the possible immunomodulatory effect by reducing tumor proliferation and metastasis.PMID:37629156 | DOI:10.3390/ijms241612972

Int J Mol Sci. 2023 Aug 18;24(16):12918. doi: 10.3390/ijms241612918.ABSTRACTAn oil palm (Elaeis guineensis Jacq.) bud rod disorder of unknown etiology, named Fatal Yellowing (FY) disease, is regarded as one of the top constraints with respect to the growth of the palm oil industry in Brazil. FY etiology has been a challenge embraced by several research groups in plant pathology throughout the last 50 years in Brazil, with no success in completing Koch's postulates. Most recently, the hypothesis of having an abiotic stressor as the initial cause of FY has gained ground, and oxygen deficiency (hypoxia) damaging the root system has become a candidate for stress. Here, a comprehensive, large-scale, single- and multi-omics integration analysis of the metabolome and transcriptome profiles on the leaves of oil palm plants contrasting in terms of FY symptomatology-asymptomatic and symptomatic-and collected in two distinct seasons-dry and rainy-is reported. The changes observed in the physicochemical attributes of the soil and the chemical attributes and metabolome profiles of the leaves did not allow the discrimination of plants which were asymptomatic or symptomatic for this disease, not even in the rainy season, when the soil became waterlogged. However, the multi-omics integration analysis of enzymes and metabolites differentially expressed in asymptomatic and/or symptomatic plants in the rainy season compared to the dry season allowed the identification of the metabolic pathways most affected by the changes in the environment, opening an opportunity for additional characterization of the role of hypoxia in FY symptom intensification. Finally, the initial analysis of a set of 56 proteins/genes differentially expressed in symptomatic plants compared to the asymptomatic ones, independent of the season, has presented pieces of evidence suggesting that breaks in the non-host resistance to non-adapted pathogens and the basal immunity to adapted pathogens, caused by the anaerobic conditions experienced by the plants, might be linked to the onset of this disease. This set of genes might offer the opportunity to develop biomarkers for selecting oil palm plants resistant to this disease and to help pave the way to employing strategies to keep the safety barriers raised and strong.PMID:37629099 | DOI:10.3390/ijms241612918

Int J Mol Sci. 2023 Aug 17;24(16):12887. doi: 10.3390/ijms241612887.ABSTRACTLipid-rich Pinus koraiensis seed kernels are highly regarded for their nutritional and health benefits. To ascertain the molecular mechanism of lipid synthesis, we conducted widely targeted metabolomic profiling together with a transcriptome analysis of the kernels in P. koraiensis cones at various developmental stages. The findings reveal that 148 different types of lipid metabolites, or 29.6% of total metabolites, are present in kernels. Among those metabolites, the concentrations of linoleic acid, palmitic acid, and α-linolenic acid were higher, and they steadily rose as the kernels developed. An additional 10 hub genes implicated in kernel lipid synthesis were discovered using weighted gene co-expression network analysis (WGCNA), gene interaction network analysis, oil body biosynthesis, and transcriptome analysis. This study used lipid metabolome and transcriptome analyses to investigate the mechanisms of key regulatory genes and lipid synthesis molecules during kernel development, which served as a solid foundation for future research on lipid metabolism and the creation of P. koraiensis kernel food.PMID:37629067 | DOI:10.3390/ijms241612887

Int J Mol Sci. 2023 Aug 16;24(16):12846. doi: 10.3390/ijms241612846.ABSTRACTAbout half a century ago, Eugene Braunwald, a father of modern cardiology, shared a revolutionary belief that "time is muscle", which predetermined never-ending effort to preserve the unaffected myocardium. In connection to that, researchers are constantly trying to better comprehend the ongoing changes of the ischemic myocardium. As the latest studies show, metabolic changes after acute myocardial infarction (AMI) are inconsistent and depend on many constituents, which leads to many limitations and lack of unification. Nevertheless, one of the promising novel mechanistic approaches related to iron metabolism now plays an invaluable role in the ischemic heart research field. The heart, because of its high levels of oxygen consumption, is one of the most susceptible organs to iron-induced damage. In the past few years, a relatively new form of programmed cell death, called ferroptosis, has been gaining much attention in the context of myocardial infarction. This review will try to summarize the main novel metabolic pathways and show the pivotal limitations of the affected myocardium metabolomics.PMID:37629039 | DOI:10.3390/ijms241612846

Int J Mol Sci. 2023 Aug 16;24(16):12849. doi: 10.3390/ijms241612849.ABSTRACTThe assembly of α-synuclein into cross-β structured amyloid fibers results in Lewy body deposits and neuronal degeneration in Parkinson's disease patients. As the cell environment is highly crowded, interactions between the formed amyloid fibers and a range of biomolecules can occur in cells. Although amyloid fibers are considered chemically inert species, recent in vitro work using model substrates has shown α-synuclein amyloids, but not monomers, to catalyze the hydrolysis of ester and phosphoester bonds. To search for putative catalytic activity of α-synuclein amyloids on biologically relevant metabolites, we here incubated α-synuclein amyloids with neuronal SH-SY5Y cell lysates devoid of proteins. LC-MS-based metabolomic (principal component and univariate) analysis unraveled distinct changes in several metabolite levels upon amyloid (but not monomer) incubation. Of 63 metabolites identified, the amounts of four increased (3-hydroxycapric acid, 2-pyrocatechuic acid, adenosine, and NAD), and the amounts of seventeen decreased (including aromatic and apolar amino acids, metabolites in the TCA cycle, keto acids) in the presence of α-synuclein amyloids. Many of these metabolite changes match what has been reported previously in Parkinson's disease patients and animal-model metabolomics studies. Chemical reactivity of α-synuclein amyloids may be a new gain-of-function that alters the metabolite composition in cells and, thereby, modulates disease progression.PMID:37629028 | DOI:10.3390/ijms241612849

Int J Mol Sci. 2023 Aug 14;24(16):12774. doi: 10.3390/ijms241612774.ABSTRACTGastric cancer (GC) typically carries a poor prognosis as it is often diagnosed at a late stage. Altered metabolism has been found to impact cancer outcomes and affect patients' quality of life, and the role of metabolites in gastric cancer prognosis has not been sufficiently understood. We aimed to establish a prognostic prediction model for GC patients based on a metabolism-associated signature and identify the unique role of metabolites in the prognosis of GC. Thus, we conducted untargeted metabolomics to detect the plasma metabolites of 218 patients with gastric adenocarcinoma and explored the metabolites related to the survival of patients with gastric cancer. Firstly, we divided patients into two groups based on the cutoff value of the abundance of each of the 60 metabolites and compared the differences using Kaplan-Meier (K-M) survival analysis. As a result, 23 metabolites associated with gastric cancer survival were identified. To establish a risk score model, we performed LASSO regression and Cox regression analysis on the 60 metabolites and identified 8 metabolites as an independent prognostic factor. Furthermore, a nomogram incorporating clinical parameters and the metabolic signature was constructed to help individualize outcome predictions. The results of the ROC curve and nomogram plot showed good predictive performance of metabolic risk features. Finally, we performed pathway analysis on the 24 metabolites identified in the two parts, and the results indicated that purine metabolism and arachidonic acid metabolism play important roles in gastric cancer prognosis. Our study highlights the important role of metabolites in the progression of gastric cancer and newly identified metabolites could be potential biomarkers or therapeutic targets for gastric cancer patients.PMID:37628957 | DOI:10.3390/ijms241612774

Int J Mol Sci. 2023 Aug 13;24(16):12751. doi: 10.3390/ijms241612751.ABSTRACTThis study aimed to assess the relationship between age-related changes in Neurofilament Light Chain (NFL), a marker of neuronal function, and various factors including muscle function, body composition, and metabolomic markers. The study included 40 participants, aged 20 to 85 years. NFL levels were measured, and muscle function, body composition, and metabolomic markers were assessed. NFL levels increased significantly with age, particularly in men. Negative correlations were found between NFL levels and measures of muscle function, such as grip strength, walking speed, and chair test performance, indicating a decline in muscle performance with increasing NFL. These associations were more pronounced in men. NFL levels also negatively correlated with muscle quality in men, as measured by 50 kHz phase angle. In terms of body composition, NFL was positively correlated with markers of fat mass and negatively correlated with markers of muscle mass, predominantly in men. Metabolomic analysis revealed significant associations between NFL levels and specific metabolites, with gender-dependent relationships observed. This study provides insights into the relationship between circulating serum NFL, muscle function, and aging. Our findings hint at circulating NFL as a potential early marker of age-associated neurodegenerative processes, especially in men.PMID:37628936 | DOI:10.3390/ijms241612751

Int J Mol Sci. 2023 Aug 13;24(16):12752. doi: 10.3390/ijms241612752.ABSTRACTHypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of medications for managing renal anemia in patients with chronic kidney disease (CKD). In addition to their erythropoietic activity, HIF-PHIs exhibit multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis through the regulation of a wide range of HIF-responsive gene expressions. However, the systemic biological effects of HIF-PHIs in CKD patients have not been fully explored. In this prospective, single-center study, we comprehensively investigated changes in plasma metabolomic profiles following the switch from an erythropoiesis-stimulating agent (ESA) to an HIF-PHI, daprodustat, in 10 maintenance hemodialysis patients. Plasma metabolites were measured before and three months after the switch from an ESA to an HIF-PHI. Among 106 individual markers detected in plasma, significant changes were found in four compounds (erythrulose, n-butyrylglycine, threonine, and leucine), and notable but non-significant changes were found in another five compounds (inositol, phosphoric acid, lyxose, arabinose, and hydroxylamine). Pathway analysis indicated decreased levels of plasma metabolites, particularly those involved in phosphatidylinositol signaling, ascorbate and aldarate metabolism, and inositol phosphate metabolism. Our results provide detailed insights into the systemic biological effects of HIF-PHIs in hemodialysis patients and are expected to contribute to an evaluation of the potential side effects that may result from long-term use of this class of drugs.PMID:37628932 | DOI:10.3390/ijms241612752

Int J Mol Sci. 2023 Aug 12;24(16):12726. doi: 10.3390/ijms241612726.ABSTRACTThis present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer Brachionus plicatilis when facing 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine biosynthesis were the top three sensitive pathways to BDE-47 exposure, which resulted in the reduction in the amino acid pool level. Pyrimidine metabolism and purine metabolism pathways were also significantly influenced, and the purine and pyrimidine content were obviously reduced in the low (0.02 mg/L) and middle (0.1 mg/L) concentration groups while increased in the high (0.5 mg/L) concentration group, evidencing the disorder of nucleotide synthesis and decomposition in B. plicatilis. The biochemical detection of the key enzymes in purine metabolism and pyrimidine metabolism showed the downregulation of Glutamine Synthetase (GS) protein expression and the elevation of Xanthine Oxidase (XOD) activity, which suggested the impaired DNA repair and ROS overproduction. The content of DNA damage biomarker (8-OHdG) increased in treatment groups, and the p53 signaling pathway was found to be activated, as indicated by the elevation of the p53 protein expression and Bax/Bcl-2 ratio. The ROS scavenger (N-acetyl-L-cysteine, NAC) addition effectively alleviated not only ROS overproduction but also DNA damage as well as the activation of apoptosis. The combined results backed up the speculation that purine metabolism and pyrimidine metabolism alteration play a pivotal role in BDE-47-induced ROS overproduction and DNA damage, and the consequent activation of the p53 signaling pathway led to the observed apoptosis in B. plicatilis.PMID:37628905 | DOI:10.3390/ijms241612726

Int J Mol Sci. 2023 Aug 12;24(16):12714. doi: 10.3390/ijms241612714.ABSTRACTThe resolution of inflammation is a complex process that is critical for removing inflammatory cells and restoring tissue function. The dysregulation of these mechanisms leads to chronic inflammatory disorders. Platelets, essential cells for preserving homeostasis, are thought to play a role in inflammation as they are a source of immunomodulatory factors. Our aim was to identify key metabolites carried by platelet-derived extracellular vesicles (PL-EVs) in a model of allergic inflammation. PL-EVs were isolated by serial ultracentrifugation using platelet-rich plasma samples obtained from platelet apheresis from severely (n = 6) and mildly (n = 6) allergic patients and non-allergic individuals used as controls (n = 8). PL-EVs were analysed by a multiplatform approach using liquid and gas chromatography coupled to mass spectrometry (LC-MS and GC-MS, respectively). PL-EVs obtained from severely and mildly allergic patients and control individuals presented comparable particle concentrations and sizes with similar protein concentrations. Strikingly, PL-EVs differed in their lipid and metabolic content according to the severity of inflammation. L-carnitine, ceramide (Cer (d18:0/24:0)), and several triglycerides, all of which seem to be involved in apoptosis and regulatory T functions, were higher in PL-EVs from patients with mild allergic inflammation than in those with severe inflammation. In contrast, PL-EVs obtained from patients with severe allergic inflammation showed an alteration in the arachidonic acid pathway. This study demonstrates that PL-EVs carry specific lipids and metabolites according to the degree of inflammation in allergic patients and propose novel perspectives for characterising the progression of allergic inflammation.PMID:37628895 | DOI:10.3390/ijms241612714

Int J Mol Sci. 2023 Aug 11;24(16):12695. doi: 10.3390/ijms241612695.ABSTRACTIn recent years, petal blight disease caused by pathogens has become increasingly epidemic in Rhododendron. Breeding disease-resistant rhododendron is considered to be a more environmentally friendly strategy than is the use of chemical reagents. In this study, we aimed to investigate the response mechanisms of rhododendron varieties to petal blight, using transcriptomics and metabolomics analyses. Specifically, we monitored changes in gene expression and metabolite accumulation in Rhododendron 'Xiaotaohong' petals infected with the Alternaria sp. strain (MR-9). The infection of MR-9 led to the development of petal blight and induced significant changes in gene transcription. Differentially expressed genes (DEGs) were predominantly enriched in the plant-pathogen interaction pathway. These DEGs were involved in carrying out stress responses, with genes associated with H2O2 production being up-regulated during the early and late stages of infection. Correspondingly, H2O2 accumulation was detected in the vicinity of the blight lesions. In addition, defense-related genes, including PR and FRK, exhibited significant up-regulated expression during the infection by MR-9. In the late stage of the infection, we also observed significant changes in differentially abundant metabolites (DAMs), including flavonoids, alkaloids, phenols, and terpenes. Notably, the levels of euscaphic acid, ganoderol A, (-)-cinchonidine, and theophylline in infected petals were 21.8, 8.5, 4.5, and 4.3 times higher, respectively, compared to the control. Our results suggest that H2O2, defense-related genes, and DAM accumulation are involved in the complex response mechanisms of Rhododendron 'Xiaotaohong' petals to MR-9 infection. These insights provide a deeper understanding of the pathogenesis of petal blight disease and may have practical implications for developing disease-resistant rhododendron varieties.PMID:37628875 | DOI:10.3390/ijms241612695

Int J Mol Sci. 2023 Aug 11;24(16):12690. doi: 10.3390/ijms241612690.ABSTRACTBreast cancer (BC) has yielded approximately 2.26 million new cases and has caused nearly 685,000 deaths worldwide in the last two years, making it the most common diagnosed cancer type in the world. BC is an intricate ecosystem formed by both the tumor microenvironment and malignant cells, and its heterogeneity impacts the response to treatment. Biomedical research has entered the era of massive omics data thanks to the high-throughput sequencing revolution, quick progress and widespread adoption. These technologies-liquid biopsy, transcriptomics, epigenomics, proteomics, metabolomics, pharmaco-omics and artificial intelligence imaging-could help researchers and clinicians to better understand the formation and evolution of BC. This review focuses on the findings of recent multi-omics-based research that has been applied to BC research, with an introduction to every omics technique and their applications for the different BC phenotypes, biomarkers, target therapies, diagnosis, treatment and prognosis, to provide a comprehensive overview of the possibilities of BC research.PMID:37628869 | DOI:10.3390/ijms241612690

Int J Mol Sci. 2023 Aug 11;24(16):12671. doi: 10.3390/ijms241612671.ABSTRACTThe aim of this study was to compare the aqueous humor (AH) and serum concentrations of metabolites in diabetic (n = 36) and nondiabetic (n = 36) senior adults undergoing cataract surgery. Blood samples were collected before surgery and AH during surgery. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted metabolomic and lipidomic analyses of samples were performed using the AbsoluteIDQ® p180 kit. Out of 188 metabolites targeted by the kit, 41 and 133 were detected in >80% of AH and serum samples, respectively. Statistical analysis performed to indicate metabolites differentiating diabetic and nondiabetic patients showed 8 and 20 significant metabolites in AH and serum, respectively. Pathway analysis performed for significant metabolites revealed that galactose metabolism is mostly affected in the AH, while arginine biosynthesis is mostly affected in the serum. Among metabolites that differentiate diabetic and nondiabetic patients, arginine was the only metabolite common to both serum and AH samples, as well as the only one with a decreased concentration in both body fluids of diabetic patients. Concentrations of the rest were elevated in AH and lowered in serum. This may suggest different mechanisms of diabetes-related dysregulation of the local metabolism in the eye in comparison to systemic changes observed in the blood.PMID:37628855 | DOI:10.3390/ijms241612671

Int J Mol Sci. 2023 Aug 11;24(16):12666. doi: 10.3390/ijms241612666.ABSTRACTTrans-10-hydroxy-2-decenoic acid (10-HDA) is a unique fatty acid found in royal jelly that possesses potential health benefits such as anti-inflammatory. However, further research is needed to fully understand its mechanisms of action and therapeutic potential for inflammation-associated diseases. In this present study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA-seq analyses were conducted to comprehensively analyze the in vitro anti-inflammatory effects of 10-HDA on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our results demonstrated that 128 differentially expressed metabolites and 1721 differentially expressed genes were identified in the 10-HDA-treated groups compared to the LPS groups. Metabolites were significantly enriched in amino acid metabolism pathways, including methionine metabolism, glycine and serine metabolism, and tryptophan metabolism. The differentially expressed genes enrichment analysis indicated that antigen processing and presentation, NOD-like receptor signaling pathway, and arginine biosynthesis were enriched with the administration of 10-had. The correlation analysis revealed that glycerophospholipid metabolism and s-adenosylmethionine-dependent methylation processes might be involved in the response to the 10-HDA treatment. Overall, the findings from this study showed that 10-HDA might involve the modulation of certain signaling pathways involved in the inflammatory response, but further research is needed to determine the safety and efficacy as a therapeutic agent.PMID:37628846 | DOI:10.3390/ijms241612666