PubMed

Artif Cells Nanomed Biotechnol. 2022 Dec;50(1):322-330. doi: 10.1080/21691401.2022.2124517.ABSTRACTThe small diameter crystalline silica is inhaled into the lung and cannot be cleared. As a result, the patient suffers from silicosis, a lung disease for which there is no effective treatment except lung transplantation. The aim of this study is to reveal the histological, cytological and metabolic characteristics of mice with pulmonary fibrosis induced by different doses of silica, and to provide an ideal animal model for drug development and disease research of pulmonary fibrosis. The experimental mice were divided into five groups. The mice were sacrificed 42 d later by nasal inhalation of normal saline and suspension containing silica 1 mg, 2 mg, 4 mg and 8 mg. Lung specimens and bronchoalveolar lavage fluid (BALF) were collected for histological and cytological examination. Carotid blood was collected and centrifuged to obtain serum for UHPLC-QE-MS non-target metabolomics detection. Compared with the normal control group, except 1 mg silica group, the other dosage groups showed different degree of disease characteristics. Metabolomics analysis showed that arginine and proline metabolism, pentose phosphate pathway, histidine metabolism, cysteine and methionine metabolism, ascorbic acid and aldoglucose metabolism were important metabolic pathways. This study reveals the histological, cytological and metabolic features of four-dose-gradient silica-induced pulmonary fibrosis mouse models.PMID:36433777 | DOI:10.1080/21691401.2022.2124517

Drug Dev Res. 2022 Nov 25. doi: 10.1002/ddr.22012. Online ahead of print.ABSTRACTRab GTPases are critical regulators of protein trafficking in the cell. To ensure proper cellular localization and function, Rab proteins must undergo a posttranslational modification, termed geranylgeranylation. In the isoprenoid biosynthesis pathway, the enzyme geranylgeranyl diphosphate synthase (GGDPS) generates the 20-carbon isoprenoid donor (geranylgeranyl pyrophosphate [GGPP]), which is utilized in the prenylation of Rab proteins. We have pursued the development of GGDPS inhibitors (GGSI) as a novel means to target Rab activity in cancer cells. Osteosarcoma (OS) and Ewing sarcoma (ES) are aggressive childhood bone cancers with stagnant survival statistics and limited treatment options. Here we show that GGSI treatment induces markers of the unfolded protein response (UPR) and triggers apoptotic cell death in a variety of OS and ES cell lines. Confirmation that these effects were secondary to cellular depletion of GGPP and disruption of Rab geranylgeranylation was confirmed via experiments using exogenous GGPP or specific geranylgeranyl transferase inhibitors. Furthermore, GGSI treatment disrupts cellular migration and invasion in vitro. Metabolomic profiles of OS and ES cell lines identify distinct changes in purine metabolism in GGSI-treated cells. Lastly, we demonstrate that GGSI treatment slows tumor growth in a mouse model of ES. Collectively, these studies support further development of GGSIs as a novel treatment for OS and ES.PMID:36433690 | DOI:10.1002/ddr.22012

Plants (Basel). 2022 Nov 12;11(22):3067. doi: 10.3390/plants11223067.ABSTRACTThe integrated analysis of different omic layers can provide new knowledge not provided by their individual analysis. This approach is also necessary to validate data and reveal post-transcriptional and post-translational mechanisms of gene expression regulation. In this work, we validated the possibility of applying this approach to non-model species such as Quercus ilex. Transcriptomics, proteomics, and metabolomics from Q. ilex seedlings subjected to drought-like conditions under the typical summer conditions in southern Spain were integrated using a non-targeted approach. Two integrative approaches, PCA and DIABLO, were used and compared. Both approaches seek to reduce dimensionality, preserving the maximum information. DIABLO also allows one to infer interconnections between the different omic layers. For easy visualization and analysis, these interconnections were analyzed using functional and statistical networks. We were able to validate results obtained by analyzing the omic layers separately. We identified the importance of protein homeostasis with numerous protease and chaperones in the networks. We also discovered new key processes, such as transcriptional control, and identified the key function of transcription factors, such as DREB2A, WRKY65, and CONSTANS, in the early response to drought.PMID:36432796 | DOI:10.3390/plants11223067

Plants (Basel). 2022 Nov 8;11(22):3014. doi: 10.3390/plants11223014.ABSTRACTLeaves of sweetpotato (Ipomoea batatas L.) are promising healthy leafy vegetable. Juvenile red fading (JRF) leaves of sweetpotato, with anthocyanins in young leaves, are good candidates for developing functional vegetables. Here, metabolic profiling and possible antioxidants were analyzed for five leaf stages of the sweetpotato cultivar "Chuanshan Zi". The contents of anthocyanins, total phenolics, and flavonoids all declined during leaf maturation, corresponding to declining antioxidant activities. By widely targeted metabolomics, we characterized 449 metabolites belonging to 23 classes. A total of 193 secondary metabolites were identified, including 82 simple phenols, 85 flavonoids, 18 alkaloids, and eight terpenes. Analysis of the metabolic data indicates that the antioxidant capacity of sweetpotato leaves is the combined result of anthocyanins and many other colorless compounds. Increased levels of "chlorogenic acid methyl ester", a compromised form of chlorogenic acid, significantly correlated with the declined antioxidant abilities. Besides anthocyanins, some significant metabolites contributing to the high antioxidant property of the sweetpotato leaves were highlighted, including chlorogenic acids, isorhamnetin glycosides, trans-4-hydroxycinnamic acid methyl ester, 4-methoxycinnamic acid, esculetin, caffeate, and trigonelline. This study provides metabolic data for the utilization of sweetpotato leaves as food sources, and sheds light on the metabolomic change for JRF leaves of other plants.PMID:36432744 | DOI:10.3390/plants11223014

Pharmaceutics. 2022 Nov 17;14(11):2496. doi: 10.3390/pharmaceutics14112496.ABSTRACTExposure to bisphenol A (BPA) is unavoidable and it has far-reaching negative effects on living systems. This study aimed to explore the toxic effects of BPA in an experimental animal model through a metabolomics approach that is useful in measuring small molecule perturbations. Beside this, we also examined the ameliorative effects of resveratrol (RSV) against BPA-induced disturbances in experimental mice. This study was conducted for 28 days, and the results showed that BPA indeed induced an impairment in amino acid metabolism, taking place in the mitochondria by significantly (p < 0.05) decreasing the levels of certain amino acids, i.e., taurine, threonine, asparagine, leucine, norleucine, and glutamic acid in the mice plasma. However, the administration of RSV did prove effective against the BPA-induced intoxication and significantly (p < 0.05) restored the level of free amino acids. Lipid metabolites, L-carnitine, sphinganine, phytosphingosine, and lysophosphatidylcholine were also determined in the mice serum. A significant (p < 0.05) decline in glutathione peroxidase (GPx), superoxide dismutase (SOD,) glutathione, and catalase levels and an elevation in malondialdehyde level in the BPA group confirmed the generation of oxidative stress and lipid peroxidation in experimental mice exposed to BPA. The expression of Carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II (CPT-II), lecithin-cholesterol acyltransferase (LCAT), carnitine O-octanoyltransferase (CROT), carnitine-acylcarnitine translocase (CACT), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes was significantly upregulated in the liver tissue homogenates of experimental mice exposed to BPA, although RSV regulated the expression of these genes when compared with BPA treated experimental mice. CPT-I, CPT-II, and CACT genes are located in the mitochondria and are involved in the metabolism and transportation of carnitine. Hence, this study confirms that BPA exposure induced oxidative stress, upregulated gene expression, and impaired lipid and amino acid metabolism in experimental mice.PMID:36432690 | DOI:10.3390/pharmaceutics14112496

Nutrients. 2022 Nov 19;14(22):4894. doi: 10.3390/nu14224894.ABSTRACTUnderstanding the inflammatory response in oral biofilm during pregnancy and its association with oral and maternal health is essential for identifying biomarker patterns that may serve as markers of pregnancy-related complications. We aimed to conduct a systematic review of the available literature to assess: (1) inflammatory responses in oral biofilm during pregnancy, (2) the association between inflammatory responses in oral biofilm during pregnancy and maternal, oral or systemic conditions, (3) changes in the response of inflammatory biomarkers found in the oral biofilm during different pregnancy stages, and (4) the value of other risk factors such as nutrition and lifestyle. PubMed, Web of Science and Cochrane Library were systematically searched from inception until April 2022. From 5441 records, 39 studies were included for qualitative assessment. The oral biofilm in pregnant women was associated with increased inflammatory biomarkers when compared to non-pregnant women. Levels of inflammatory biomarkers in the oral biofilm were found to be highest in pregnant women with systemic conditions. Increased inflammatory biomarkers in the oral biofilm were also associated with worse oral health outcomes. Given the importance of nutrition and lifestyle for pregnancy and oral health outcomes and the fact that these factors were largely excluded in the included studies, future research should consider a holistic view of the mother during pregnancy to capture physiological, hormonal, immunologic, and metabolic changes in the context of inflammatory responses.PMID:36432584 | DOI:10.3390/nu14224894

Nutrients. 2022 Nov 16;14(22):4850. doi: 10.3390/nu14224850.ABSTRACTTo further explore and improve the mechanism of probiotics to alleviate the disorder of lipid metabolism, transcriptomic and metabolomic with bioinformatic analysis were combined. In the present study, we successfully established a rat model of lipid metabolism disorder using a high-fat diet. Intervention with Lactobacillus rhamnosus hsryfm 1301 fermented milk resulted in a significant reduction in body weight, serum free fatty acid and blood lipid levels (p < 0.05), which predicted that the lipid metabolism disorder was alleviated in rats. Metabolomics and transcriptomics identified a total of 33 significantly different metabolites and 183 significantly different genes screened in the intervention group compared to the model group. Comparative analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations identified a total of 61 pathways in which differential metabolites and genes were jointly involved, with linoleic acid metabolism, glycine, serine and threonine metabolism and glutamatergic synapse in both transcriptome and metabolome being found to be significantly altered (p < 0.05). Lactobacillus rhamnosus hsryfm 1301 fermented milk was able to directly regulate lipid metabolism disorders by regulating the metabolic pathways of linoleic acid metabolism, glycerophospholipid metabolism, fatty acid biosynthesis, alpha-linolenic acid metabolism, fatty acid degradation, glycerolipid metabolism and arachidonic acid metabolism. In addition, we found that Lactobacillus rhamnosus hsryfm 1301 fermented milk indirectly regulates lipid metabolism through regulating amino acid metabolism, the nervous system, the endocrine system and other pathways. Lactobacillus rhamnosus hsryfm 1301 fermented milk could alleviate the disorders of lipid metabolism caused by high-fat diet through multi-target synergy.PMID:36432537 | DOI:10.3390/nu14224850

Nutrients. 2022 Nov 15;14(22):4828. doi: 10.3390/nu14224828.ABSTRACTThe fermented tea beverage Kombucha is obtained through a series of biochemical and enzymatic reactions carried out by symbiotic cultures of bacteria and yeasts (SCOBY). It contains organic acids, vitamins, amino acids, and biologically active compounds, notably polyphenols, derived mainly from tea. Kombucha exhibits a range of health-promoting properties, including antioxidant or detoxifying effects. This fermented beverage is traditionally brewed with black tea, but other types of tea are used increasingly, which may have significant implications in terms of chemical composition and health-promoting effects. In this preliminary study, we investigated the content of micronutrients (manganese (Mn), copper (Cu), iron (Fe), chromium (Cr) and zinc (Zn)) by the ICP-OES method in Kombucha prepared with black, red, green and white tea at different time points of fermentation (1, 7, 14 days). It should be noted that the composition of separate ingredients such as tea, leaven or sugar has not been studied. Kombucha had the highest content of zinc-0.36 mg/L to 2.08 mg/L, which accounts for between 3% and 26% of the RDA (Recommended Dietary Allowance) for adults, and the smallest amounts of chromium (0.03 mg/L to 0.09 mg/L), which however represents as much as between 75% and 232% of the RDA. It has been demonstrated that the type of tea as well as the day of fermentation have a significant effect on the concentrations of selected minerals. Kombucha can therefore supplement micronutrients in the human diet.PMID:36432515 | DOI:10.3390/nu14224828

Nutrients. 2022 Nov 12;14(22):4794. doi: 10.3390/nu14224794.ABSTRACTThe identification of molecular biomarkers that can be used to quantitatively link dietary intake to phenotypic traits in humans is a key theme in modern nutritional research. Although dairy products (with and without fermentation) represent a major food group, the identification of markers of their intake lags behind that of other food groups. Here, we report the results from an analysis of the metabolites in postprandial serum and urine samples from a randomized crossover study with 14 healthy men who ingested acidified milk, yogurt, and a non-dairy meal. Our study confirms the potential of lactose and its metabolites as markers of lactose-containing dairy foods and the dependence of their combined profiles on the fermentation status of the consumed products. Furthermore, indole-3-lactic acid and 3-phenyllactic acid are two products of fermentation whose postprandial behaviour strongly discriminates yogurt from milk intake. Our study also provides evidence of the ability of milk fermentation to increase the acute delivery of free amino acids to humans. Notably, 3,5-dimethyloctan-2-one also proves to be a specific marker for milk and yogurt consumption, as well as for cheese consumption (previously published data). These molecules deserve future characterisation in human interventional and observational studies.PMID:36432479 | DOI:10.3390/nu14224794

Molecules. 2022 Nov 21;27(22):8102. doi: 10.3390/molecules27228102.ABSTRACTHigh altitude hypoxia stress is the key cause of high-altitude pulmonary edema and spleen contraction. The molecular mechanism of immune response of various tissue systems to hypoxia stress remains lacking. In this study, we applied proteomics combined with metabolomics to explore the key molecular profilings involved in high altitude hypoxia response in the spleen of mice. The results showed that 166 proteins were significantly up-regulated, and only 39 proteins were down-regulated. Bioinformatics analysis showed that mineral absorption, neuroactive ligand-receptor interaction, arachidonic acid metabolism, IL-17 signaling pathway and NOD-like preceptor signaling pathway were significantly enriched in the list of 166 upregulated differentially expressed proteins (DEPs). Among these metabolic pathways, the former three pathways were co-identified in KEGG terms from LC-MS/MS based metabolic analysis. We further found that both arachidonate 15-lipoxygenase and hematopoietic prostaglandin D synthase were upregulated by around 30% and 80% for their protein levels and mRNA levels, respectively. Most downstream metabolites were upregulated accordingly, such as prostaglandin A2 and D2. This study provides important evidence that arachidonic acid metabolism potentially promotes spleen hypoxia response through a combined analysis of proteomics and metabolism, which could bring new insights for the spleen targeted rational design upon arachidonic acid metabolism of new therapies.PMID:36432203 | DOI:10.3390/molecules27228102

Molecules. 2022 Nov 21;27(22):8086. doi: 10.3390/molecules27228086.ABSTRACTThe lichen species Lecania brialmontii, Pseudephebe pubescens, and Sphaerophorus globosus are part of the prominent lichenoflora of the Antarctic territory. In this work, we report the metabolomic identification of ethanolic extracts of these species, their antioxidant and cholinesterase enzyme inhibitory activity, and conduct a molecular docking analysis with typical compounds. Eighteen compounds were identified by UHPLC-ESI-QTOF-MS in L. brialmontii, 18 compounds in P. pubescens, and 14 compounds in S. globosus. The content of phenolic compounds was variable among the species, ranging from 0.279 to 2.821 mg AG/g, and all three species showed high inhibition potential on the cholinesterase enzymes. Molecular docking showed important interactions between AChE and BChE with the selected compounds. This study evidences the chemical fingerprint of three species of the order Lecanorales that support the continuation of the study of other biological activities and their potential for medical research.PMID:36432187 | DOI:10.3390/molecules27228086

Molecules. 2022 Nov 20;27(22):8068. doi: 10.3390/molecules27228068.ABSTRACTHost inflammatory responses are key to protection against injury; however, persistent inflammation is detrimental and contributes to morbidity and mortality. Herein, we demonstrated the anti-inflammatory role of Arteannuin-B (1) and its new spirocyclic-2-isoxazoline derivative JR-9 and their side effects in acute inflammatory condition in vivo using LPS-induced cytokines assay, carrageenan-induced paw edema, acetic acid-induced writhing and tail immersion. The results show that the spirocyclic-2-isoxazoline derivative is a potent anti-inflammatory agent with minimal cell toxicity as compared to Arteannuin-B. In addition, the efficacies of these compounds were also validated by flow cytometric, computational, and histopathological analysis. Our results show that the anti-inflammatory response of JR-9 significantly reduces the ability of mouse macrophages to produce NO, TNF-α, and IL-6 following LPS stimulation. Therefore, JR-9 is a prospective candidate for the development of anti-inflammatory drugs and its molecular mechanism is likely related to the regulation of NF-κB and MAPK signaling pathway.PMID:36432169 | DOI:10.3390/molecules27228068

Molecules. 2022 Nov 18;27(22):8013. doi: 10.3390/molecules27228013.ABSTRACTMetabolomics have been widely used in pregnancy-related diseases. However, physiological variations induced by chronic hypoxia during pregnancy are not well characterized. We aimed to investigate physiological variations induced by chronic hypoxia during pregnancy. A Sprague-Dawley (SD) pregnant rat model of chronic hypoxia was established. Plasma and urine metabolite profiles at different stages of the pregnancy were detected by 1H NMR (nuclear magnetic resonance). Multivariate statistical analysis was used to analyze changes in plasma and urine metabolic trajectories at different time-points. We identified hypoxia-induced changes in the levels of 30 metabolites in plasma and 29 metabolites in urine during different stages of pregnancy; the prominently affected metabolites included acetic acid, acetone, choline, citric acid, glutamine, isoleucine, lysine, and serine. Most significant hypoxia-induced changes in plasma and urine sample metabolites were observed on the 11th day of gestation. In summary, chronic hypoxia has a significant effect on pregnant rats, and may cause metabolic disorders involving glucose, lipids, amino acids, and tricarboxylic acid cycle. Metabolomics study of the effect of hypoxia during pregnancy may provide insights into the pathogenesis of obstetric disorders.PMID:36432114 | DOI:10.3390/molecules27228013

Molecules. 2022 Nov 16;27(22):7937. doi: 10.3390/molecules27227937.ABSTRACTThe liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach is a powerful technology for discovering novel biologically active molecules. In this study, we investigated the metabolic profiling of Orchidaceae species using LC-HRMS/MS data combined with chemometric methods and dereplication tools to discover antifungal compounds. We analyze twenty ethanolic plant extracts from Vanda and Cattleya (Orchidaceae) genera. Molecular networking and chemometric methods were used to discriminate ions that differentiate healthy and fungal-infected plant samples. Fifty-three metabolites were rapidly annotated through spectral library matching and in silico fragmentation tools. The metabolomic profiling showed a large production of polyphenols, including flavonoids, phenolic acids, chromones, stilbenoids, and tannins, which varied in relative abundance across species. Considering the presence and abundance of metabolites in both groups of samples, we can infer that these constituents are associated with biochemical responses to microbial attacks. In addition, we evaluated the metabolic dynamic through the synthesis of stilbenoids in fungal-infected plants. The tricin derivative flavonoid- and the loliolide terpenoidfound only in healthy plant samples, are promising antifungal metabolites. LC-HRMS/MS, combined with state-of-the-art tools, proved to be a rapid and reliable technique for fingerprinting medicinal plants and discovering new hits and leads.PMID:36432039 | DOI:10.3390/molecules27227937

Molecules. 2022 Nov 16;27(22):7929. doi: 10.3390/molecules27227929.ABSTRACTBACKGROUND: Carfilzomib (Cfz) is an anti-cancer drug related to cardiorenal adverse events, with cardiovascular and renal complications limiting its clinical use. Despite the important progress concerning the discovery of the underlying causes of Cfz-induced nephrotoxicity, the molecular/biochemical background is still not well clarified. Furthermore, the number of metabolomics-based studies concerning Cfz-induced nephrotoxicity is limited.METHODS: A metabolomics UPLC-HRMS-DIA methodology was applied to three bio-sample types i.e., plasma, kidney, and urine, obtained from two groups of mice, namely (i) Cfz (8 mg Cfz/ kg) and (ii) Control (0.9% NaCl) (n = 6 per group). Statistical analysis, involving univariate and multivariate tools, was applied for biomarker detection. Furthermore, a sub-study was developed, aiming to estimate metabolites' correlation among bio-samples, and to enlighten potential mechanisms.RESULTS: Cfz mostly affects the kidneys and urine metabolome. Fifty-four statistically important metabolites were discovered, and some of them have already been related to renal diseases. Furthermore, the correlations between bio-samples revealed patterns of metabolome alterations due to Cfz.CONCLUSIONS: Cfz causes metabolite retention in kidney and dysregulates (up and down) several metabolites associated with the occurrence of inflammation and oxidative stress.PMID:36432029 | DOI:10.3390/molecules27227929

Molecules. 2022 Nov 16;27(22):7917. doi: 10.3390/molecules27227917.ABSTRACTFermented bean products are used worldwide; most of the products are made using only a few kinds of beans. However, the metabolite changes and contents in the beans generally used during fermentation are unrevealed. Therefore, we selected four different beans (soybean, Glycine max, GM; wild soybean, Glycine soja, GS; common bean, Phaseolus vulgaris, PV; and hyacinth bean, Lablab purpureus, LP) that are the most widely consumed and fermented with Aspergillus oryzae. Then, metabolome and multivariate statistical analysis were performed to figure out metabolite changes during fermentation. In the four beans, carbohydrates were decreased, but amino acids and fatty acids were increased in the four beans as they fermented. The relative amounts of amino acids were relatively abundant in fermented PV and LP as compared to other beans. In contrast, isoflavone aglycones (e.g., daidzein, glycitein, and genistein) and DDMP-conjugated soyasaponins (e.g., soyasaponins βa and γg) were increased in GM and GS during fermentation. Notably, these metabolite changes were more significant in GS than GM. In addition, the increase of antioxidant activity in fermented GS was significant compared to other beans. We expect our research provides a basis to extend choice for bean fermentation for consumers and food producers.PMID:36432017 | DOI:10.3390/molecules27227917

Molecules. 2022 Nov 13;27(22):7830. doi: 10.3390/molecules27227830.ABSTRACTBile acids play a significant role in the digestion of nutrients. In addition, bile acids perform a signaling function through their blood-circulating fraction. They regulate the activity of nuclear and membrane receptors, located in many tissues. The gut microbiota is an important factor influencing the effects of bile acids via enzymatic modification. Depending on the rate of healthy and pathogenic microbiota, a number of bile acids may support lipid and glucose homeostasis as well as shift to more toxic compounds participating in many pathological conditions. Thus, bile acids can be possible biomarkers of human pathology. However, the chemical structure of bile acids is similar and their analysis requires sensitive and specific methods of analysis. In this review, we provide information on the chemical structure and the biosynthesis of bile acids, their regulation, and their physiological role. In addition, the review describes the involvement of bile acids in various diseases of the digestive system, the approaches and challenges in the analysis of bile acids, and the prospects of their use in omics technologies.PMID:36431930 | DOI:10.3390/molecules27227830

Molecules. 2022 Nov 10;27(22):7758. doi: 10.3390/molecules27227758.ABSTRACTToad venom, a dried product of secretion from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has had the therapeutic effects of hepatocellular carcinoma confirmed. Bufalin and cinobufagin were considered as the two most representative antitumor active components in toad venom. However, the underlying mechanisms of this antitumor effect have not been fully implemented, especially the changes in endogenous small molecules after treatment. Therefore, this study was designed to explore the intrinsic mechanism on hepatocellular carcinoma after the cotreatment of bufalin and cinobufagin based on untargeted tumor metabolomics. Ultraperformance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was performed to identify the absorbed components of toad venom in rat plasma. In vitro experiments were determined to evaluate the therapeutic effects of bufalin and cinobufagin and screen the optimal ratio between them. An in vivo HepG2 tumor-bearing nude mice model was established, and a series of pharmacodynamic indicators were determined, including the body weight of mice, tumor volume, tumor weight, and histopathological examination of tumor. Further, the entire metabolic alterations in tumor after treating with bufalin and cinobufagin were also profiled by UHPLC-MS/MS. Twenty-seven active components from toad venom were absorbed in rat plasma. We found that the cotreatment of bufalin and cinobufagin exerted significant antitumor effects both in vitro and in vivo, which were reflected in inhibiting proliferation and inducing apoptosis of HepG2 cells and thereby causing cell necrosis. After cotherapy of bufalin and cinobufagin for twenty days, compared with the normal group, fifty-six endogenous metabolites were obviously changed on HepG2 tumor-bearing nude mice. Meanwhile, the abundance of α-linolenic acid and phenethylamine after the bufalin and cinobufagin intervention was significantly upregulated, which involved phenylalanine metabolism and α-linolenic acid metabolism. Furthermore, we noticed that amino acid metabolites were also altered in HepG2 tumor after drug intervention, such as norvaline and Leu-Ala. Taken together, the cotreatment of bufalin and cinobufagin has significant antitumor effects on HepG2 tumor-bearing nude mice. Our work demonstrated that the in-depth mechanism of antitumor activity was mainly through the regulation of phenylalanine metabolism and α-Linolenic acid metabolism.PMID:36431859 | DOI:10.3390/molecules27227758

Molecules. 2022 Nov 8;27(22):7683. doi: 10.3390/molecules27227683.ABSTRACTCicadae Periostracum (CP) is a traditional Chinese medicinal herb derived from the slough that is molted from the nymph of the insect Cryptotympana pustulata Fabricius. Washing with water to remove residual silt is a primary processing method of CP that is recommended by the Chinese Pharmacopoeia, but how washing methods affect the quality and bioactivity of CP is unknown. In this study, the quality and bioactivity of non-washed CP (CP-NW), post-molting-washed CP (CP-WAT), and pre-molting-washed CP (CP-WBT) were comparatively investigated. The quality of these CP samples was evaluated in terms of the UPLC-QTOF-MS/MS-based chemical profiling and semi-quantification of 39 N-acetyldopamine oligomers (belonging to six chemical types), the HPLC-UV-based quantification of 17 amino acids, the ICP-MS-based quantification of four heavy metals, and the contents of ash; the bioactivities of the samples were compared regarding their anti-oxidant and anti-inflammatory activities. It was found that, compared with CP-NW, both CP-WBT and CP-WAT had significantly lower contents of ash and heavy metals. Moreover, compared with CP-WAT, CP-WBT contained lower levels of total ash, acid-insoluble ash, and heavy metals and higher contents of N-acetyldopamine oligomers and amino acids. It also had enhanced anti-oxidant and anti-inflammatory activities. A Spearman's correlation analysis found that the contents of N-acetyldopamine oligomers and free amino acids were positively correlated with the anti-oxidant/-inflammatory activities of CP. All these results suggest that pre-molting washing can not only remove the residual silt but can also avoid the loss of the bioactive components and assure higher bioactivities. It is concluded that pre-molting washing could enhance the quality and bioactivity of CP and should be a superior alternative method for the primary processing of qualified CP.PMID:36431784 | DOI:10.3390/molecules27227683

J Clin Med. 2022 Nov 15;11(22):6745. doi: 10.3390/jcm11226745.ABSTRACTAntiblastic drugs-induced cardiomyopathy remains a relevant cause of morbidity and mortality, during and after chemotherapy, despite the progression in protective therapy against cardiovascular diseases and myocardial function. In the last few decades, many groups of researchers have focused their attention on studying the metabolic profile, first in animals, and, subsequently, in humans, looking for profiles which could be able to predict drug-induced cardiotoxicity and cardiovascular damage. In clinical practice, patients identified as being at risk of developing cardiotoxicity undergo a close follow-up and more tailored therapies. Injury to the heart can be a consequence of both new targeted therapies, such as tyrosine kinase inhibitors, and conventional chemotherapeutic agents, such as anthracyclines. This review aims to describe all of the studies carried on this topic of growing interest.PMID:36431222 | DOI:10.3390/jcm11226745