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Foods (Basel, Switzerland) Apr 2024Yellowhorn ( Bunge) is a unique oilseed tree in China with high edible and medicinal value. However, the application potential of yellowhorn has not been adequately...
Yellowhorn ( Bunge) is a unique oilseed tree in China with high edible and medicinal value. However, the application potential of yellowhorn has not been adequately explored. In this study, widely targeted metabolomics (HPLC-MS/MS and GC-MS) and network pharmacology were applied to investigate the nutritional potential of yellowhorn leaves and flowers. The widely targeted metabolomics results suggested that the yellowhorn leaf contains 948 non-volatile metabolites and 638 volatile metabolites, while the yellowhorn flower contains 976 and 636, respectively. A non-volatile metabolite analysis revealed that yellowhorn leaves and flowers contain a variety of functional components beneficial to the human body, such as terpenoids, flavonoids, alkaloids, lignans and coumarins, phenolic acids, amino acids, and nucleotides. An analysis of volatile metabolites indicated that the combined action of various volatile compounds, such as 2-furanmethanol, β-icon, and 2-methyl-3-furanthiol, provides the special flavor of yellowhorn leaves and flowers. A network pharmacology analysis showed that various components in the flowers and leaves of yellowhorn have a wide range of biological activities. This study deepens our understanding of the non-volatile and volatile metabolites in yellowhorn and provides a theoretical basis and data support for the whole resource application of yellowhorn.
PubMed: 38672945
DOI: 10.3390/foods13081274 -
Foods (Basel, Switzerland) Apr 2024Sesame seeds ( L.) have been cultivated for thousands of years and have long been celebrated for their culinary versatility. Beyond their delightful nutty flavor and... (Review)
Review
Sesame seeds ( L.) have been cultivated for thousands of years and have long been celebrated for their culinary versatility. Beyond their delightful nutty flavor and crunchy texture, sesame seeds have also gained recognition for their remarkable health benefits. This article provides an in-depth exploration of the numerous ways in which sesame seeds contribute to overall well-being. Sesame seeds are a powerhouse of phytochemicals, including lignans derivatives, tocopherol isomers, phytosterols, and phytates, which have been associated with various health benefits, including the preservation of cardiovascular health and the prevention of cancer, neurodegenerative disorders, and brain dysfunction. These compounds have also been substantiated for their efficacy in cholesterol management. Their potential as a natural source of beneficial plant compounds is presented in detail. The article further explores the positive impact of sesame seeds on reducing the risk of chronic diseases thanks to their rich polyunsaturated fatty acids content. Nevertheless, it is crucial to remember the significance of maintaining a well-rounded diet to achieve the proper balance of n-3 and n-6 polyunsaturated fatty acids, a balance lacking in sesame seed oil. The significance of bioactive polypeptides derived from sesame seeds is also discussed, shedding light on their applications as nutritional supplements, nutraceuticals, and functional ingredients. Recognizing the pivotal role of processing methods on sesame seeds, this review discusses how these methods can influence bioactive compounds. While roasting the seeds enhances the antioxidant properties of the oil extract, certain processing techniques may reduce phenolic compounds.
PubMed: 38672826
DOI: 10.3390/foods13081153 -
Frontiers in Genetics 2024Shading treatments impact the tea ( L.) quality. The sunlight sensitive varieties can be grown under shading nets for better growth and secondary metabolite content....
Shading treatments impact the tea ( L.) quality. The sunlight sensitive varieties can be grown under shading nets for better growth and secondary metabolite content. Here, we studied the responses of a sunlight sensitive green tea variety "Huangjinya" by growing under colored shading nets (red, yellow, blue, and black (75% and 95%) shading rates) to find out the most suitable color of the shading net. Red shading was the most promising treatment as it positively affected the weight and length of 100 one-bud-three leaves and reduced the degree and rate of new shoots burn compared to control (natural sunlight). We then explored the comparative metabolomic changes in response to red shading by using UPLC-ESI-MS/MS system. The amino acids and derivatives, flavonoids, and alkaloids were downaccumulated whereas lipids, organic acids, and lignans were upaccumulated in Red shade grown tea samples. The red shading nets caused a decreased catechin, epicatechin, dopamine, and L-tyramine contents but increased caffeine content. We then employed transcriptome sequencing to find key changes in expressions of related genes and pathways. Notably, key genes associated with the phenylpropanoid and flavonoid biosynthesis pathways exhibited complex regulation. These expression changes suggested a potential trend of polymerization or condensation of simple molecules like catechin or pelargonidin into larger molecules like glucoside or proanthocyanidins. Here, Red shading net triggered higher expression of genes enriched in lipid biosynthesis and jasmonic acid biosynthesis, suggesting an interplay of fatty acids and JA in improving tea performance. These findings contribute to the metabolic responses of Huangjinya tea to red shading nets which might have implications for flavor and health benefits. Our data provide a foundation for further exploration and optimization of cultivation practices for this unique tea variety.
PubMed: 38660681
DOI: 10.3389/fgene.2024.1365243 -
BMC Cancer Apr 2024Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective...
BACKGROUND
Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective treatment currently. Proteolysis-targeting chimeric molecules (PROTACs) may provide new therapeutic avenues for treatment of podophyllotoxin derivatives-resistant SCLC with LM, warranting further exploration.
METHODS
The SCLC cell line H128 expressing luciferase were mutated by MNNG to generate H128-Mut cell line. After subcutaneous inoculation of H128-Mut into nude mice, H128-LM and H128-BPM (brain parenchymal metastasis) cell lines were primarily cultured from LM and BPM tissues individually, and employed to in vitro drug testing. The SCLC-LM mouse model was established by inoculating H128-LM into nude mice via carotid artery and subjected to in vivo drug testing. RNA-seq and immunoblotting were conducted to uncover the molecular targets for LM.
RESULTS
The SCLC-LM mouse model was successfully established, confirmed by in vivo live imaging and histological examination. The upregulated genes included EZH2, SLC44A4, VEGFA, etc. in both BPM and LM cells, while SLC44A4 was particularly upregulated in LM cells. When combined with PROTAC EZH2 degrader-1, the drug sensitivity of cisplatin, etoposide (VP16), and teniposide (VM26) for H128-LM was significantly increased in vitro. The in vivo drug trials with SCLC-LM mouse model demonstrated that PROTAC EZH2 degrader-1 plus VM26 or cisplatin/ VP16 inhibited H128-LM tumour significantly compared to VM26 or cisplatin/ VP16 alone (P < 0.01).
CONCLUSION
The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM.
Topics: Animals; Small Cell Lung Carcinoma; Mice; Humans; Lung Neoplasms; Drug Resistance, Neoplasm; Enhancer of Zeste Homolog 2 Protein; Podophyllotoxin; Cell Line, Tumor; Mice, Nude; Meningeal Carcinomatosis; Xenograft Model Antitumor Assays; Proteolysis
PubMed: 38644473
DOI: 10.1186/s12885-024-12244-3 -
Journal of Neuropathology and... Jun 2024Cognitive dysfunction following anesthesia with agents such as sevoflurane is a significant clinical problem, particularly in elderly patients. This study aimed to...
Cognitive dysfunction following anesthesia with agents such as sevoflurane is a significant clinical problem, particularly in elderly patients. This study aimed to explore the protective effects of the phytochemical syringaresinol (SYR) against sevoflurane-induced cognitive deficits in aged Sprague-Dawley rats and to determine the underlying mechanisms involved. We assessed the impact of SYR on sevoflurane-induced cognitive impairment, glial activation, and neuronal apoptosis through behavioral tests (Morris water maze), immunofluorescence, Western blotting for key proteins involved in apoptosis and inflammation, and enzyme-linked immunosorbent assays for interleukin-1β, tumor necrosis factor-α, and interleukin-6. SYR treatment mitigated sevoflurane-induced cognitive decline, reduced microglial and astrocyte activation (decreased Iba-1 and GFAP expression), and countered neuronal apoptosis (reduced Bax, cleaved-caspase3, and cleaved-PARP expression). SYR also enhanced Sirtuin-1 (SIRT1) expression and reduced p-Tau phosphorylation; these effects were reversed by the SIRT1 inhibitor EX527. SYR exerts neuroprotective effects on sevoflurane-induced cognitive dysfunction by modulating glial activity, apoptotic signaling, and Tau phosphorylation through the SIRT1 pathway. These findings could inform clinical strategies to safeguard cognitive function in patients undergoing anesthesia.
Topics: Animals; Sevoflurane; tau Proteins; Rats, Sprague-Dawley; Cognitive Dysfunction; Rats; Phosphorylation; Male; Anesthetics, Inhalation; Furans; Neuroprotective Agents; Lignans; Aging; Apoptosis
PubMed: 38622895
DOI: 10.1093/jnen/nlae026 -
Scientific Reports Apr 2024Sect. tuberculata plant belongs to the Camellia genus and is named for the "tuberculiform protuberance on the surface of the ovary and fruit". It is a species of great...
Extensive targeted metabolomics analysis reveals the identification of major metabolites, antioxidants, and disease-resistant active pharmaceutical components in Camellia tuberculata (Camellia L.) seeds.
Sect. tuberculata plant belongs to the Camellia genus and is named for the "tuberculiform protuberance on the surface of the ovary and fruit". It is a species of great ornamental value and potential medicinal value. However, little has been reported on the metabolites of C. tuberculata seeds. Therefore, this study was conducted to investigate the metabolites of C. tuberculata seeds based on UPLC/ESI-Q TRAP-MS/MS with extensively targeted metabolomics. A total of 1611 metabolites were identified, including 107 alkaloids, 276 amino acids and derivatives, 283 flavonoids, 86 lignans and coumarins, 181 lipids, 68 nucleotides and derivatives, 101 organic acids, 190 phenolic acids, 10 quinones, 4 steroids, 17 tannins, 111 terpenoids, and 177 other metabolites. We compared the different metabolites in seeds between HKH, ZM, ZY, and LY. The 1311 identified different metabolites were classified into three categories. Sixty-three overlapping significant different metabolites were found, of which lignans and coumarins accounted for the largest proportion. The differentially accumulated metabolites were enriched in different metabolic pathways between HKH vs. LY, HKH vs. ZM, HKH vs. ZY, LY vs. ZY, ZM vs. LY and ZM vs. ZY, with the most abundant metabolic pathways being 4, 2, 4, 7, 7 and 5, respectively (p < 0.05). Moreover, among the top 20 metabolites in each subgroup comparison in terms of difference multiplicity 7, 8 and 13. ZM and ZY had the highest phenolic acid content. Ninety-six disease-resistant metabolites and 48 major traditional Chinese medicine agents were identified based on seven diseases. The results of this study will not only lead to a more comprehensive and in-depth understanding of the metabolic properties of C. tuberculata seeds, but also provide a scientific basis for the excavation and further development of its medicinal value.
Topics: Camellia; Antioxidants; Tandem Mass Spectrometry; Flavonoids; Seeds; Metabolomics; Plant Extracts; Lignans; Coumarins; Hydroxybenzoates
PubMed: 38622262
DOI: 10.1038/s41598-024-58725-0 -
Nutrients Apr 2024The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles.... (Review)
Review
The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles. We conducted a literature review of longitudinal studies on the association of diet with gut microbiota in adult populations and extracted those dietary components with evidence of beneficial or unfavorable effects. Dietary recall data from the National Health and Nutrition Examination Survey (NHANES, 2005-2010, = 3812) were used to compute the DI-GM, and associations with biomarkers of gut microbiota diversity (urinary enterodiol and enterolactone) were examined using linear regression. From a review of 106 articles, 14 foods or nutrients were identified as components of the DI-GM, including fermented dairy, chickpeas, soybean, whole grains, fiber, cranberries, avocados, broccoli, coffee, and green tea as beneficial components, and red meat, processed meat, refined grains, and high-fat diet (≥40% of energy from fat) as unfavorable components. Each component was scored 0 or 1 based on sex-specific median intakes, and scores were summed to develop the overall DI-GM score. In the NHANES, DI-GM scores ranged from 0-13 with a mean of 4.8 (SE = 0.04). Positive associations between DI-GM and urinary enterodiol and enterolactone were observed. The association of the novel DI-GM with markers of gut microbiota diversity demonstrates the potential utility of this index for gut health-related studies.
Topics: Adult; Female; Male; Humans; Gastrointestinal Microbiome; Nutrition Surveys; Diet, High-Fat; Meat; 4-Butyrolactone; Lignans
PubMed: 38613077
DOI: 10.3390/nu16071045 -
Molecules (Basel, Switzerland) Mar 2024Podophyllotoxin, a cyclolignan natural product, has been the object of extensive chemomodulation to obtain better chemotherapeutic agents. Among the obtained...
Podophyllotoxin, a cyclolignan natural product, has been the object of extensive chemomodulation to obtain better chemotherapeutic agents. Among the obtained podophyllotoxin derivatives, podophyllic aldehyde showed very interesting potency and selectivity against several tumoral cell lines, so it became our lead compound for further modifications, as described in this work, oriented toward the enlargement of the cyclolignan skeleton. Thus, modifications performed at the aldehyde function included nucleophilic addition reactions and the incorporation of the aldehyde carbon into several five-membered rings, such as thiazolidinones and benzo-fused azoles. The synthesized derivatives were evaluated against several types of cancer cells, and although some compounds were cytotoxic at the nanomolar range, most of them were less potent and less selective than the parent compound podophyllic aldehyde, with the most potent being those having the lactone ring of podophyllotoxin. In silico ADME evaluation predicted good druggability for most of them. The results indicate that the γ-lactone ring is important for potency, while the α,β-unsaturated aldehyde is necessary to induce selectivity in these cyclolignans.
Topics: Humans; Podophyllotoxin; Antineoplastic Agents; Skeleton; Hypertrophy; Aldehydes; Lactones; Radiopharmaceuticals
PubMed: 38611722
DOI: 10.3390/molecules29071442 -
Chemico-biological Interactions May 2024Bruceantinol (BOL), isolated from the dried fruit of the Brucea javanica (L.) Merr., exhibits cytotoxic effects on breast cancer cells. However, the underlying mechanism...
Bruceantinol (BOL), isolated from the dried fruit of the Brucea javanica (L.) Merr., exhibits cytotoxic effects on breast cancer cells. However, the underlying mechanism remains to be fully addressed. In this paper, the MCF-7 and MDA-MB-231 human breast cancer cell lines were used as experimental models to uncover how BOL inhibits breast cancer cell growth. The effects of BOL on cell growth, proliferation, the cell cycle, and apoptosis were investigated using the MTT assays, EdU incorporation assays, and flow cytometry, respectively. Bioinformatics techniques were applied to predict the key targets of BOL in breast cancer. Subsequent validation of these targets and the anti-breast cancer mechanism of BOL was conducted through Western blotting, RT-PCR, siRNA transfection, and molecular docking analysis. The results demonstrated that BOL dose- and time-dependently reduced the growth of both cell lines, impeded cell proliferation, disrupted the cell cycle, and induced necrosis in MCF-7 cells and apoptosis in MDA-MB-231 cells. Furthermore, CDK2/4/6 were identified as BOL targets, and their knockdown reduced cell sensitivity to BOL. BOL was found to potentially bind with CDK2/4/6 to facilitate protein degradation through the proteasome pathway. Additionally, BOL activated ERK in MDA-MB-231 cells, and this activation was required for BOL's functions in these cells. Collectively, BOL may act as an inhibitor of CDK2/4/6 to exert anti-breast cancer effects. Its effects on cell growth and CDK2/4/6 expression may also depend on ERK activation in HRsHER2 breast cancer cells. These results suggest the potential of using BOL for treating breast cancer.
Topics: Humans; Breast Neoplasms; Cell Proliferation; Cyclin-Dependent Kinase 2; Apoptosis; Female; Cell Line, Tumor; Cyclin-Dependent Kinase 6; Molecular Docking Simulation; Cyclin-Dependent Kinase 4; MCF-7 Cells; Lignans; Cell Cycle; Protein Kinase Inhibitors
PubMed: 38608999
DOI: 10.1016/j.cbi.2024.110999 -
BMC Plant Biology Apr 2024Mango (Mangifera indica L.) is grown in Hainan, Guangdong, Yunnan, Sichuan, and Fujian provinces and Guanxi autonomous region of China. However, trees growing in these...
BACKGROUND
Mango (Mangifera indica L.) is grown in Hainan, Guangdong, Yunnan, Sichuan, and Fujian provinces and Guanxi autonomous region of China. However, trees growing in these areas suffer severe cold stress during winter, which affects the yield. To this regard, data on global metabolome and transcriptome profiles of leaves are limited. Here, we used combined metabolome and transcriptome analyses of leaves of three mango cultivars with different cold stress tolerance, i.e. Jinhuang (J)-tolerant, Tainung (T) and Guiremang No. 82 (G)-susceptible, after 24 (LF), 48 (MF) and 72 (HF) hours of cold.
RESULTS
A total of 1,323 metabolites belonging to 12 compound classes were detected. Of these, amino acids and derivatives, nucleotides and derivatives, and lipids accumulated in higher quantities after cold stress exposure in the three cultivars. Notably, Jinhuang leaves showed increasing accumulation trends of flavonoids, terpenoids, lignans and coumarins, and alkaloids with exposure time. Among the phytohormones, jasmonic acid and abscisic acid levels decreased, while N6-isopentenyladenine increased with cold stress time. Transcriptome analysis led to the identification of 22,526 differentially expressed genes. Many genes enriched in photosynthesis, antenna proteins, flavonoid, terpenoid (di- and sesquiterpenoids) and alkaloid biosynthesis pathways were upregulated in Jihuang leaves. Moreover, expression changes related to phytohormones, MAPK (including calcium and HO), and the ICE-CBF-COR signalling cascade indicate involvement of these pathways in cold stress responses.
CONCLUSION
Cold stress tolerance in mango leaves is associated with regulation of primary and secondary metabolite biosynthesis pathways. Jasmonic acid, abscisic acid, and cytokinins are potential regulators of cold stress responses in mango leaves.
Topics: Transcriptome; Cold-Shock Response; Mangifera; Plant Growth Regulators; Abscisic Acid; Hydrogen Peroxide; China; Gene Expression Profiling; Gene Expression Regulation, Plant; Cyclopentanes; Oxylipins
PubMed: 38600447
DOI: 10.1186/s12870-024-04983-z