PubMed

Int J Mol Sci. 2023 Apr 25;24(9):7818. doi: 10.3390/ijms24097818.ABSTRACTPatients with metabolic syndrome are often prescribed statins to prevent the development of cardiovascular disease. Conversely, data on their effects on non-alcoholic steatohepatitis (NASH) are lacking. We evaluated these effects by feeding APOE*3-Leiden mice a Western-type diet (WTD) with or without atorvastatin to induce NASH and hepatic fibrosis. Besides the well-known plasma cholesterol lowering (-30%) and anti-atherogenic effects (severe lesion size -48%), atorvastatin significantly reduced hepatic steatosis (-22%), the number of aggregated inflammatory cells in the liver (-80%) and hepatic fibrosis (-92%) compared to WTD-fed mice. Furthermore, atorvastatin-treated mice showed less immunohistochemically stained areas of inflammation markers. Atorvastatin prevented accumulation of free cholesterol in the form of cholesterol crystals (-78%). Cholesterol crystals are potent inducers of the NLRP3 inflammasome pathway and atorvastatin prevented its activation, which resulted in reduced expression of the pro-inflammatory cytokines interleukin (IL)-1β (-61%) and IL-18 (-26%). Transcriptome analysis confirmed strong reducing effects of atorvastatin on inflammatory mediators, including NLRP3, NFκB and TLR4. The present study demonstrates that atorvastatin reduces hepatic steatosis, inflammation and fibrosis and prevents cholesterol crystal formation, thereby precluding NLRP3 inflammasome activation. This may render atorvastatin treatment as an attractive approach to reduce NAFLD and prevent progression into NASH in dyslipidemic patients.PMID:37175538 | DOI:10.3390/ijms24097818

Int J Mol Sci. 2023 Apr 24;24(9):7768. doi: 10.3390/ijms24097768.ABSTRACTKorean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the impacts of darkness and different light wavelengths on the metabolomics and anti-cancer activity of ginseng extracts. Hydroponically-grown Korean ginseng was shifted to a light-emitting diodes (LEDs) chamber for blue-LED and darkness treatments, while white fluorescent (FL) light treatment was the control. MCF-7 breast cancer and lipopolysaccharide (LPS)-induced BV-2 microglial cells were used to determine chemo-preventive and neuroprotective potential. Overall, 53 significant primary metabolites were detected in the treated samples. The levels of ginsenosides Rb1, Rb2, Rc, Rd, and Re, as well as organic and amino acids, were significantly higher in the dark treatment, followed by blue-LED treatment and the FL control. The dark-treated ginseng extract significantly induced apoptotic signaling in MCF-7 cells and dose-dependently inhibited the NF-κB and MAP kinase pathways in LPS-induced BV-2 cells. Short-term dark treatment increased the content of Rd, Rc, Rb1, Rb2, and Re ginsenosides in ginseng extracts, which promoted apoptosis of MCF-7 cells and inhibition of the MAP kinase pathway in BV-2 microglial cells. These results indicate that the dark treatment might be effective in improving the pharmacological potential of ginseng.PMID:37175475 | DOI:10.3390/ijms24097768

Int J Mol Sci. 2023 Apr 24;24(9):7761. doi: 10.3390/ijms24097761.ABSTRACTObesity is a chronic and complex disease, with an increasing incidence worldwide that is associated with metabolic disorders such as type 2 diabetes mellitus (T2DM). Thus, it is important to determine the differences between metabolically healthy obese individuals and those with metabolic disorders. The aim of this study was to perform an untargeted metabolomics assay in women with morbid obesity (MO) compared to a normal weight group, and to differentiate the metabolome of these women with MO who present with T2DM. We carried out a liquid chromatography-mass spectrometry-based untargeted metabolomics assay using serum samples of 209 Caucasian women: 73 with normal weight and 136 with MO, of which 71 had T2DM. First, we found increased levels of choline and acylglycerols and lower levels of bile acids, steroids, ceramides, glycosphingolipids, lysophosphatidylcholines, and lysophosphatidylethanolamines in MO women than in the control group. Then, in MO women with T2DM, we found increased levels of glutamate, propionyl-carnitine, bile acids, ceramides, lysophosphatidylcholine 14:0, phosphatidylinositols and phosphoethanolamines, and lower levels of Phe-Ile/Leu. Thus, we found metabolites with opposite trends of concentration in the two metabolomic analyses. These metabolites could be considered possible new factors of study in the pathogenesis of MO and associated T2DM in women.PMID:37175468 | DOI:10.3390/ijms24097761

Molecules. 2023 May 8;28(9):3967. doi: 10.3390/molecules28093967.ABSTRACT(1) Background: Citrus honey constitutes a unique monofloral honey characterized by a distinctive aroma and unique taste. The non-targeted chemical analysis can provide pivotal information on chemical markers that differentiate honey based on its geographical and botanical origin. (2) Methods: Within the PRIMA project "PLANT-B", a metabolomics workflow was established to unveil potential chemical markers of orange blossom honey produced in case study areas of Egypt, Italy, and Greece. In some of these areas, aromatic medicinal plants were cultivated to enhance biodiversity and attract pollinators. The non-targeted chemical analysis and metabolomics were conducted using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). (3) Results: Forty compounds were disclosed as potential chemical markers, enabling the differentiation of the three orange blossom honeys according to geographical origin. Italian honey showed a preponderance of flavonoids, while in Greek honey, terpenoids and iridoids were more abundant than flavonoids, except for hesperidin. In Egyptian honey, suberic acid and a fatty acid ester derivative emerged as chemical markers. New, for honey, furan derivatives were identified using GC-MS in Greek samples. (4) Conclusions: The application of UHPLC-HRMS metabolomics combined with an elaborate melissopalynological analysis managed to unveil several potential markers of Mediterranean citrus honey potentially associated with citrus crop varieties and the local indigenous flora.PMID:37175378 | DOI:10.3390/molecules28093967

Molecules. 2023 May 4;28(9):3886. doi: 10.3390/molecules28093886.ABSTRACTThe aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the metabolic responses of both triple-negative MDA-MB-231 cells and hormone-responsive MCF-7 cells to treatment with these phenols. Notably, while some effects were common across both cell types, others were dependent on the cell type, highlighting the importance of cellular metabolic phenotype. Common effects included stimulation of mitochondrial metabolism, acetate production, and formate overflow. On the other hand, glucose metabolism and lactate production were differentially modulated. HT and LUT appeared to inhibit glycolysis and promote the hexosamine biosynthetic pathway in MDA-MB-231 cells, while MCF-7 cells exhibited higher glycolytic flux when treated with phenolic compounds. Another significant difference was observed in lipid metabolism. Treated MDA-MB-231 cells displayed increased levels of neutral lipids (likely stored in cytosolic droplets), whereas treatment of MCF-7 cells with HT led to a decrease in triacylglycerols. Additionally, glutathione levels increased in MDA-MB-231 cells treated with HT or LUT, as well as in MCF-7 cells treated with LUT. In contrast, in HT-treated MCF-7 cells, glutathione levels decreased, indicating different modulation of cellular redox status. Overall, this work provides new insights into the metabolic impact of HT and LUT on different BC cell subtypes, paving the way for a better understanding of the nutritional relevance of these phenolic compounds in the context of BC prevention and management.PMID:37175295 | DOI:10.3390/molecules28093886

Molecules. 2023 Apr 30;28(9):3840. doi: 10.3390/molecules28093840.ABSTRACTSkeletal muscle is closely linked to energy metabolism, but it is inevitably deprived of energy. Cellular differentiation is an essential and energy-demanding process in skeletal muscle development. Much attention has been paid to identifying beneficial factors that promote skeletal muscle satellite cell differentiation and further understanding the underlying regulatory mechanisms. As a critical metabolic substrate or regulator, α-ketoglutarate (AKG) has been recognized as a potential nutritional supplement or therapeutic target for skeletal muscle. We have previously found beneficial effects of AKG supplementation on the proliferation of C2C12 myoblasts cultured under both normal and energy-deficient conditions and have further elucidated the underlying metabolic mechanisms. However, it remains unclear what role AKG plays in myotube formation in different energy states. In the present study, we investigated the effects of AKG supplementation on the differentiation of C2C12 myoblasts cultured in normal medium (Nor myotubes) and low glucose medium (Low myotubes) and performed NMR-based metabonomic profiling to address AKG-induced metabolic changes in both Nor and Low myotubes. Significantly, AKG supplementation promoted myotube formation and induced metabolic remodeling in myotubes under normal medium and low glucose medium, including improved energy metabolism and enhanced antioxidant capacity. Specifically, AKG mainly altered amino acid metabolism and antioxidant metabolism and upregulated glycine levels and antioxidase expression. Our results are typical for the mechanistic understanding of the effects of AKG supplementation on myotube formation in the two energy states. This study may be beneficial for further exploring the applications of AKG supplementation in sports, exercise, and therapy.PMID:37175250 | DOI:10.3390/molecules28093840

Molecules. 2023 Apr 30;28(9):3830. doi: 10.3390/molecules28093830.ABSTRACTSweet peppers are consumed worldwide, and traditional uses have sparked interest in their applications as dietary antioxidants, which can be enhanced in plants using elicitors. These are endowed with phytochemicals with potential health benefits such as antioxidants, bioavailability, and bioaccessibility. The trend in metabolomics shows us chemical fingerprints linking metabolomics, innovative analytical form, and bioinformatics tools. The objective was to evaluate the impact of multiple stress interactions, elicitor concentrations, and electrical conductivity on the concentration of secondary metabolites to relate their response to metabolic pathways through the foliar application of a cocktail of said elicitors in pepper crops under greenhouse conditions. The extracts were analyzed by spectrophotometry and gas chromatography, and it was shown that the PCA analysis identified phenolic compounds and low molecular weight metabolites, confirming this as a metabolomic fingerprint in the hierarchical analysis. These compounds were also integrated by simultaneous gene and metabolite simulants to obtain effect information on different metabolic pathways. Showing changes in metabolite levels at T6 (36 mM H2O2 and 3.6 dS/m) and T7 (0.1 mM SA and 3.6 dS/m) but showing statistically significant changes at T5 (3.6 dS/m) and T8 (0.1 mM SA, 36 mM H2O2, and 3.6 dS/m) compared to T1 (32 dS/m) or control. Six pathways changed significantly (p < 0.05) in stress-induced treatments: aminoacyl t-RNA and valine-leucine-isoleucine biosynthesis, and alanine-aspartate-glutamate metabolism, glycoxylate-dicarboxylate cycle, arginine-proline, and citrate. This research provided a complete profile for the characterization of metabolomic fingerprint of bell pepper under multiple stress conditions.PMID:37175241 | DOI:10.3390/molecules28093830

Molecules. 2023 Apr 30;28(9):3828. doi: 10.3390/molecules28093828.ABSTRACT3,4,5,4'-Trans-tetramethoxystilbene (Synonyms: DMU-212) is a resveratrol analogue with stronger antiproliferative activity and more bioavailability. However, the metabolite characterization of this component remains insufficient. An efficient strategy was proposed for the comprehensive in vivo metabolite profiling of DMU-212 after oral administration in ApcMin/+ mice based on the effectiveness of the medicine. Ultra-high performance liquid chromatography-quadrupole/orbitrap/linear ion trap mass spectrometry (UHPLC-Q/Orbitrap/LTQ MS) in the AcquireXTM intelligent data acquisition mode, combining the exact mass and structural information, was established for the profiling and identification of the metabolites of DMU-212 in vivo, and the possible metabolic pathways were subsequently proposed after the oral dose of 240mg/kg for 3 weeks in the colorectal adenoma (CRA) spontaneous model ApcMin/+ mice. A total of 63 metabolites of DMU-212 were tentatively identified, including 48, 48, 34 and 28 metabolites in the ApcMin/+ mice's intestinal contents, liver, serum, and colorectal tissues, respectively. The metabolic pathways, including demethylation, oxidation, desaturation, methylation, acetylation, glucuronide and cysteine conjugation were involved in the metabolism. Additionally, further verification of the representative active metabolites was employed using molecular docking analysis. This study provides important information for the further investigation of the active constituents of DMU-212 and its action mechanisms for CRA prevention.PMID:37175240 | DOI:10.3390/molecules28093828

Molecules. 2023 Apr 27;28(9):3759. doi: 10.3390/molecules28093759.ABSTRACTCoix lachryma-jobi L. is an excellent plant resource that has a concomitant function for medicine, foodstuff and forage in China. At present, the commonly used cultivar for both medicine and foodstuff is Xiaobaike, and the cultivar for foraging is Daheishan. However, differences in the internal composition of plants lead to the expression of different phenotypic traits. In order to comprehensively elucidate the differences in nutrient composition changes in Coix seeds, a non-targeted metabolomics method based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) was used to analyze the metabolic changes in Coix seeds at different developmental stages. An edible Coix relative (Xiaobaike) and a feeding Coix relative (Daheishan) were selected as the research subjects. In the metabolome analysis of Coix seed, 314 metabolites were identified and detected, among which organic acids, carbohydrates, lipids, nucleotides and flavonoids were the main components. As an important standard for evaluating the quality of Coix seed, seven lipids were detected, among which fatty acids included not only even-chain fatty acids, but also odd-chain fatty acids, which was the first time detecting a variety of odd-chain fatty acids in Coix seed. The analysis of the compound contents in edible and feeding-type Coix lachryma-jobi L. and the lipid content at the mature stage showed that, among them, arachidic acid, behenic acid, heptadecanoic acid, heneicosanoic acid and pristanic acid may be the key compounds affecting the lipid content. In addition, in the whole process of semen coicis maturation, edible and feeding Coix show similar trends, and changes in the third period show clear compounds in the opposite situation, suggesting that edible and feeding Coix not only guarantee the relative stability of species but also provide raw materials for genetic breeding. This study provides valuable information on the formation of the edible and medicinal qualities of Coix.PMID:37175169 | DOI:10.3390/molecules28093759

Molecules. 2023 Apr 26;28(9):3734. doi: 10.3390/molecules28093734.ABSTRACTTetrahydrocurcumin (THC) is a metabolite of curcumin (CUR). It shares many of CUR's beneficial biological activities in addition to being more water-soluble, chemically stable, and bioavailable compared to CUR. However, its mechanisms of action have not been fully elucidated. This paper addresses the preventive role of THC on various brain dysfunctions as well as its effects on brain redox processes, traumatic brain injury, ischemia-reperfusion injury, Alzheimer's disease, and Parkinson's disease in various animal or cell culture models. In addition to its strong antioxidant properties, the effects of THC on the reduction of amyloid β aggregates are also well documented. The therapeutic potential of THC to treat patterns of mitochondrial brain dysmorphic dysfunction is also addressed and thoroughly reviewed, as is evidence from experimental studies about the mechanism of mitochondrial failure during cerebral ischemia/reperfusion injury. THC treatment also results in a dose-dependent decrease in ERK-mediated phosphorylation of GRASP65, which prevents further compartmentalization of the Golgi apparatus. The PI3K/AKT signaling pathway is possibly the most involved mechanism in the anti-apoptotic effect of THC. Overall, studies in various animal models of different brain disorders suggest that THC can be used as a dietary supplement to protect against traumatic brain injury and even improve brain function in Alzheimer's and Parkinson's diseases. We suggest further preclinical studies be conducted to demonstrate the brain-protective, anti-amyloid, and anti-Parkinson effects of THC. Application of the methods used in the currently reviewed studies would be useful and should help define doses and methods of THC administration in different disease conditions.PMID:37175144 | DOI:10.3390/molecules28093734

Diagnostics (Basel). 2023 Apr 25;13(9):1542. doi: 10.3390/diagnostics13091542.ABSTRACTIntrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.PMID:37174934 | DOI:10.3390/diagnostics13091542

Diagnostics (Basel). 2023 Apr 24;13(9):1528. doi: 10.3390/diagnostics13091528.ABSTRACTAcute respiratory distress syndrome (ARDS) is a rapidly progressive form of respiratory failure that accounts for 10% of admissions to the ICU and is associated with approximately 40% mortality in severe cases. Despite significant mortality and healthcare burden, the mainstay of management remains supportive care. The recent pandemic of SARS-CoV-2 has re-ignited a worldwide interest in exploring the pathophysiology of ARDS, looking for innovative ideas to treat this disease. Recently, many trials have been published utilizing different pharmacotherapy targets; however, the long-term benefits of these agents remain unknown. Metabolomics profiling and stem cell transplantation offer strong enthusiasm and may completely change the outlook of ARDS management in the near future.PMID:37174920 | DOI:10.3390/diagnostics13091528

Cells. 2023 Apr 24;12(9):1228. doi: 10.3390/cells12091228.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a multi-systemic, incurable, amyloid disease affecting the motor neurons, resulting in the death of patients. The disease is either sporadic or familial with SOD1, C9orf72, FUS, and TDP-43 constituting the majority of familial ALS. Multi-omics studies on patients and model systems like mice and yeast have helped in understanding the association of various signaling and metabolic pathways with the disease. The yeast model system has played a pivotal role in elucidating the gene amyloid interactions. We carried out an integrated transcriptomic and metabolomic analysis of the TDP-43 expressing yeast model to elucidate deregulated pathways associated with the disease. The analysis shows the deregulation of the TCA cycle, single carbon metabolism, glutathione metabolism, and fatty acid metabolism. Transcriptomic analysis of GEO datasets of TDP-43 expressing motor neurons from mice models of ALS and ALS patients shows considerable overlap with experimental results. Furthermore, a yeast model was used to validate the obtained results using metabolite addition and gene knock-out experiments. Taken together, our result shows a potential role for the TCA cycle, cellular redox pathway, NAD metabolism, and fatty acid metabolism in disease. Supplementation of reduced glutathione, nicotinate, and the keto diet might help to manage the disease.PMID:37174628 | DOI:10.3390/cells12091228

Animals (Basel). 2023 May 4;13(9):1539. doi: 10.3390/ani13091539.ABSTRACTTo investigate the key gut microbiota and metabolites associated with the growth performance of Macrobrachium rosenbergii families, 16S rRNA sequencing and LC-MS metabolomic methods were used. In this study, 90 M. rosenbergii families were bred to evaluate growth performance. After 92 days of culture, high (H), medium (M), and low (L) experimental groups representing three levels of growth performance, respectively, were collected according to the weight gain and specific growth rate of families. The composition of gut microbiota showed that the relative abundance of Firmicutes, Lachnospiraceae, Lactobacillus, and Blautia were much higher in Group H than those in M and L groups. Meanwhile, compared to the M and L groups, Group H had significantly higher levels of spermidine, adenosine, and creatinine, and lower levels of L-citrulline. Correlation analysis showed that the abundances of Lactobacillus and Blautia were positively correlated with the levels of alpha-ketoglutaric acid and L-arginine. The abundance of Blautia was also positively correlated with the levels of adenosine, taurine, and spermidine. Notably, lots of metabolites related to the metabolism and biosynthesis of arginine, taurine, hypotaurine, and fatty acid were upregulated in Group H. This study contributes to figuring out the landscape of the gut microbiota and metabolites associated with prawn growth performance and provides a basis for selective breeding.PMID:37174576 | DOI:10.3390/ani13091539

Animals (Basel). 2023 Apr 23;13(9):1440. doi: 10.3390/ani13091440.ABSTRACTIn order to explore the metabolic and ionic changes of hoof-deformed cows, the serum samples of 10 healthy cows (group C) and 10 hoof-deformed cows (group T) were analyzed by LC-MS/MS and ICP-OES/MS. The pathway enrichment of differential metabolites was analyzed by screening and identifying differential metabolites and ions and using a bioinformatics method. The integration of metabolomics and ionics was analyzed with ggplot2 software in R language, and verified by MRM target metabolomics. The results showed that 127 metabolites were screened by metabolomics, of which 81 were up-regulated (p < 0.05) and 46 were down-regulated (p < 0.05). The results of ICP-OES/MS showed that 13 kinds of ions such as K, Li, and Pb in serum of dairy cows were up-regulated, while 18 kinds of ions such as Al, Cu and Sb were down-regulated. The integrated analysis of metabolomics and ionics found that potassium ions were positively correlated with L-tyrosine, L-proline, thiamine and L-valine. Sodium ions were positively correlated with L-valine and negatively correlated with α-D-glucose. The results of high-throughput target metabolomics showed that the contents of L-proline, L-phenylalanine and L-tryptophan in serum of dairy cows increased significantly, which was consistent with the results of non-target metabolomics. In a word, the metabolism and ion changes in dairy cows with hoof deformation were revealed by metabolomics and ionics.PMID:37174477 | DOI:10.3390/ani13091440

Foods. 2023 Apr 23;12(9):1751. doi: 10.3390/foods12091751.ABSTRACTThe State Council of China has called for the comprehensive development and utilization of Acer truncatum resources. However, research on one of its by-products, namely seed oil residue (ASR), from seed oil extraction is seriously insufficient, resulting in a waste of these precious resources. We aimed to optimize the conditions of ultrasound-assisted extraction (UAE) using a response surface methodology to obtain high acetylcholinesterase (AChE) inhibitory components from ASR and to tentatively identify the active metabolites in ASR using non-targeted metabolomics. Based on the results of the independent variables test, the interaction effects of three key extracting variables, including methanol concentration, ultrasonic time, and material-to-liquid ratio, were further investigated using the Box-Behnken design (BBD) to obtain prior active components with high AChE inhibitory activity. UPLC-QTOF-MS combined with a multivariate method was used to analyze the metabolites in ASR and investigate the causes of activity differences. Based on the current study, the optimal conditions for UAE were as follows: methanol concentration of 85.06%, ultrasonic time of 39.1 min, and material-to-liquid ratio of 1.06:10 (g/mL). Under these optimal conditions, the obtained extracts show strong inhibitions against AChE with half maximal inhibitory concentration (IC50) values ranging from 0.375 to 0.459 µg/mL according to an Ellman's method evaluation. Furthermore, 55 metabolites were identified from the ASR extracted using methanol in different concentrations, and 9 biomarkers were subsequently identified as potential compounds responsible for the observed AChE inhibition. The active extracts have potential to be used for the development of functional foods with positive effects on Alzheimer's disease owing to their high AChE inhibition activity. Altogether, this study provides insights into promoting the comprehensive utilization of A. truncatum resources.PMID:37174291 | DOI:10.3390/foods12091751

Foods. 2023 Apr 22;12(9):1737. doi: 10.3390/foods12091737.ABSTRACTBeauty tea with special flavor can be affected by the degree of leafhopper puncturing. The present research adopted widely targeted metabolomics to analyze the characteristic metabolites of fresh tea leaves and beauty tea with different degrees of leafhopper puncturing. Low-puncturing beauty tea (LPBT) exhibited a superior quality. Altogether, 95 and 65 differential metabolites, including tea polyphenols, saccharides, and lipids, were identified from fresh leaves and beauty tea, respectively. The partial least squares regression (PLSR) analysis results showed that isomaltulose, theaflavic acid, and ellagic acid, may be the characteristic metabolites that form the different taste outlines of beauty tea. Based on odor activity values (OAVs) and partial least squares discriminant analysis (PLS-DA), dihydrolinalool and cis-linalool oxide were identified as characteristic volatile components, which may be essential for the formation of the different aroma characteristic of beauty tea. The results provide a theoretical basis for selecting raw materials, performing quality research, and developing beauty tea industrially.PMID:37174277 | DOI:10.3390/foods12091737

Cancers (Basel). 2023 May 3;15(9):2593. doi: 10.3390/cancers15092593.ABSTRACTDue to the severe toxicity posed by chemotherapeutic drugs, adjuvant nutritional intervention has gained increased attention in the treatment of pancreatic cancer (PC). Amino acid (AA) metabolism is aberrantly regulated in PC and circulating histidine (His) levels are low in PC patients. We hypothesized that His uptake and/or metabolism is dysregulated in PC and that combining His with gemcitabine (Gem), a drug used in the treatment of PC, will enhance the anti-cancer effects of Gem. We performed in vitro and in vivo studies to determine the anticancer effect of the combination of His and Gem against lethal PC. We demonstrate that circulating His levels are low in both human subjects and genetically engineered mice exhibiting pancreatic tumors. Interestingly, the expression of histidine ammonia lyase, an enzyme involved in His catabolism, is higher in PC compared to normal subjects. His + Gem exerts a more potent cytotoxic effect in PC cells compared to individual treatments. His treatment results in a profound increase in His accumulation, accompanied by a depletion of a number of AAs, promoting cancer cell survival and/or glutathione (GSH) synthesis. His but not Gem increases hydrogen peroxide and depletes cellular GSH. Supplementation with GSH protects cells against His + Gem-induced cytotoxicity. Further, our in vivo studies demonstrate that His + Gem potently reduced tumor mass and improved mouse survival. Taken together, our data suggest that PC cells exhibit an aberrant His uptake/accumulation which, in turn, leads to oxidative stress and depletion of AA pool, thereby enhancing the anticancer effect of Gem.PMID:37174059 | DOI:10.3390/cancers15092593

Cancers (Basel). 2023 Apr 28;15(9):2539. doi: 10.3390/cancers15092539.ABSTRACTThe human microbiome represents the diversity of microorganisms that live together at different organ sites, influencing various physiological processes and leading to pathological conditions, even carcinogenesis, in case of a chronic imbalance. Additionally, the link between organ-specific microbiota and cancer has attracted the interest of numerous studies and projects. In this review article, we address the important aspects regarding the role of gut, prostate, urinary and reproductive system, skin, and oral cavity colonizing microorganisms in prostate cancer development. Various bacteria, fungi, virus species, and other relevant agents with major implications in cancer occurrence and progression are also described. Some of them are assessed based on their values of prognostic or diagnostic biomarkers, while others are presented for their anti-cancer properties.PMID:37174009 | DOI:10.3390/cancers15092539

J Cheminform. 2023 May 12;15(1):52. doi: 10.1186/s13321-023-00724-w.ABSTRACTMetabolomics experiments generate highly complex datasets, which are time and work-intensive, sometimes even error-prone if inspected manually. Therefore, new methods for automated, fast, reproducible, and accurate data processing and dereplication are required. Here, we present UmetaFlow, a computational workflow for untargeted metabolomics that combines algorithms for data pre-processing, spectral matching, molecular formula and structural predictions, and an integration to the GNPS workflows Feature-Based Molecular Networking and Ion Identity Molecular Networking for downstream analysis. UmetaFlow is implemented as a Snakemake workflow, making it easy to use, scalable, and reproducible. For more interactive computing, visualization, as well as development, the workflow is also implemented in Jupyter notebooks using the Python programming language and a set of Python bindings to the OpenMS algorithms (pyOpenMS). Finally, UmetaFlow is also offered as a web-based Graphical User Interface for parameter optimization and processing of smaller-sized datasets. UmetaFlow was validated with in-house LC-MS/MS datasets of actinomycetes producing known secondary metabolites, as well as commercial standards, and it detected all expected features and accurately annotated 76% of the molecular formulas and 65% of the structures. As a more generic validation, the publicly available MTBLS733 and MTBLS736 datasets were used for benchmarking, and UmetaFlow detected more than 90% of all ground truth features and performed exceptionally well in quantification and discriminating marker selection. We anticipate that UmetaFlow will provide a useful platform for the interpretation of large metabolomics datasets.PMID:37173725 | DOI:10.1186/s13321-023-00724-w