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1.
Drug Des Devel Ther ; 18: 1175-1188, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645986

RESUMEN

Purpose: Many herbs can promote neurological recovery following traumatic brain injury (TBI). There must lie a shared mechanism behind the common effectiveness. We aimed to explore the key therapeutic targets for TBI based on the common effectiveness of the medicinal plants. Material and methods: The TBI-effective herbs were retrieved from the literature as imputes of network pharmacology. Then, the active ingredients in at least two herbs were screened out as common components. The hub targets of all active compounds were identified through Cytohubba. Next, AutoDock vina was used to rank the common compound-hub target interactions by molecular docking. A highly scored compound-target pair was selected for in vivo validation. Results: We enrolled sixteen TBI-effective medicinal herbs and screened out twenty-one common compounds, such as luteolin. Ten hub targets were recognized according to the topology of the protein-protein interaction network of targets, including epidermal growth factor receptor (EGFR). Molecular docking analysis suggested that luteolin could bind strongly to the active pocket of EGFR. Administration of luteolin or the selective EGFR inhibitor AZD3759 to TBI mice promoted the recovery of body weight and neurological function, reduced astrocyte activation and EGFR expression, decreased chondroitin sulfate proteoglycans deposition, and upregulated GAP43 levels in the cortex. The effects were similar to those when treated with the selective EGFR inhibitor. Conclusion: The common effectiveness-based, common target screening strategy suggests that inhibition of EGFR can be an effective therapy for TBI. This strategy can be applied to discover core targets and therapeutic compounds in other diseases.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Simulación del Acoplamiento Molecular , Farmacología en Red , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/metabolismo , Animales , Ratones , Plantas Medicinales/química , Masculino , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Luteolina/farmacología , Luteolina/química , Ratones Endogámicos C57BL , Humanos
2.
Inorg Chem ; 63(16): 7464-7472, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38598182

RESUMEN

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C9H7O2)2·UO2 (denoted as UO2-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.


Asunto(s)
Cinamatos , Uranio , Cinamatos/química , Cinamatos/farmacología , Animales , Ligandos , Ratones , Uranio/química , Uranio/metabolismo , Uranio/toxicidad , Riñón/efectos de los fármacos , Riñón/metabolismo , Línea Celular , Teoría Funcional de la Densidad , Ratas , Estructura Molecular , Supervivencia Celular/efectos de los fármacos , Quelantes/química , Quelantes/farmacología , Quelantes/síntesis química
3.
Fitoterapia ; 175: 105921, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38561052

RESUMEN

Sophoridine, which is derived from the Leguminous plant Sophora alopecuroides L., has certain pharmacological activity as a new anticancer drug. Herein, a series of novel N-substituted sophoridine derivatives was designed, synthesized and evaluated with anticancer activity. Through QSAR prediction models, it was discovered that the introduction of a benzene ring as a main pharmacophore and reintroduced into a benzene in para position on the phenyl ring in the novel sophoridine derivatives improved the anticancer activity effectively. In vitro, 28 novel compounds were evaluated for anticancer activity against four human tumor cell lines (A549, CNE-2, HepG-2, and HEC-1-B). In particular, Compound 26 exhibited remarkable inhibitory effects, with an IC50 value of 15.6 µM against HepG-2 cells, surpassing cis-Dichlorodiamineplatinum (II). Molecular docking studies verified that the derivatives exhibit stronger binding affinity with DNA topoisomerase I compared to sophoridine. In addition, 26 demonstrated significant inhibition of DNA Topoisomerase I and could arrest cells in G0/G1 phase. This study provides valuable insights into the design and synthesis of N-substituted sophoridine derivatives with anticancer activity.

4.
Nat Metab ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561509

RESUMEN

Disruption of circadian rhythm during pregnancy produces adverse health outcomes in offspring; however, the role of maternal circadian rhythms in the immune system of infants and their susceptibility to inflammation remains poorly understood. Here we show that disruption of circadian rhythms in pregnant mice profoundly aggravates the severity of neonatal inflammatory disorders in both male and female offspring, such as necrotizing enterocolitis and sepsis. The diminished maternal production of docosahexaenoic acid (DHA) and the impaired immunosuppressive function of neonatal myeloid-derived suppressor cells (MDSCs) contribute to this phenomenon. Mechanistically, DHA enhances the immunosuppressive function of MDSCs via PPARγ-mediated mitochondrial oxidative phosphorylation. Transfer of MDSCs or perinatal supplementation of DHA relieves neonatal inflammation induced by maternal rhythm disruption. These observations collectively demonstrate a previously unrecognized role of maternal circadian rhythms in the control of neonatal inflammation via metabolic reprograming of myeloid cells.

5.
BMC Complement Med Ther ; 24(1): 145, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575994

RESUMEN

BACKGROUND: Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. METHODS: The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. RESULTS: Ginger significantly reduced the m6A level of OC cells SKOV3. The 3'UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. CONCLUSIONS: Ginger inhibits ovarian cancer cells' SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.


Asunto(s)
Neoplasias Ováricas , Zingiber officinale , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Metilación de ARN , Antígeno B7-H1 , Claudinas
6.
Proc Natl Acad Sci U S A ; 121(14): e2317574121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38530899

RESUMEN

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.


Asunto(s)
Contaminantes Atmosféricos , Enfermedades Mitocondriales , Humanos , Contaminantes Atmosféricos/análisis , Fosforilcolina , Material Particulado/análisis , Pulmón , Carbono/análisis , Monitoreo del Ambiente
7.
Diabetol Metab Syndr ; 16(1): 18, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38216955

RESUMEN

BACKGROUND: Diabetes mellitus (DM) and its associated vascular complications have become a worldwide health concern. The effects and mechanism of vitamin D supplementation on endothelial function under high glucose condition remain elusive. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with 35 mM glucose, then 100 nM vitamin D were added. Transwell migration assay, CCK-8, immunofluorescence, flow cytometry, autophagy flux and transmission electric microscope were performed. RESULTS: Vitamin D reduced apoptosis, promoted migration and enhanced viability of HUVECs, decreased TIPE1 (Tumor necrosis factor-α-induced protein 8-like 1) under high glucose conditions. Overexpression of TIPE1 reverses the effects of vitamin D by increasing ROS production, inflammation, cell apoptosis, and suppressing autophagy, cell migration and viability. And vitamin D negatively correlated with TIPE1 mRNA level in DM patients. CONCLUSIONS: Vitamin D reverses the harmful effects of high glucose on HUVECs by reducing TIPE1 expression. And vitamin D supplementation could help to alleviate high glucose-induced injury in type 2 diabetes mellitus patients with microvascular complications.

8.
CNS Neurosci Ther ; 30(3): e14231, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37183394

RESUMEN

INTRODUCTION: Spatial changes of amine metabolites and histopathology of the whole brain help to reveal the mechanism of traumatic brain injury (TBI) and treatment. METHODS: A newly developed liquid microjunction surface sampling-tandem mass tag-ultra performance liquid chromatography-mass spectrometry technique is applied to profile brain amine metabolites in five brain regions after impact-induced TBI at the subacute stage. H&E, Nissl, and immunofluorescence staining are performed to spatially correlate microscopical changes to metabolic alterations. Then, bioinformatics, molecular docking, ELISA, western blot, and immunofluorescence are integrated to uncover the mechanism of Xuefu Zhuyu decoction (XFZYD) against TBI. RESULTS: Besides the hippocampus and cortex, the thalamus, caudate-putamen, and fiber tracts also show differentiated metabolic changes between the Sham and TBI groups. Fourteen amine metabolites (including isomers such as L-leucine and L-isoleucine) are significantly altered in specific regions. The metabolic changes are well matched with the degree of neuronal damage, glia activation, and neurorestoration. XFZYD reverses the dysregulation of several amine metabolites, such as hippocampal Lys-Phe/Phe-Lys and dopamine. Also, XFZYD enhances post-TBI angiogenesis in the hippocampus and the thalamus. CONCLUSION: This study reveals the local amine-metabolite and histological changes in the subacute stage of TBI. XFZYD may promote TBI recovery by normalizing amine metabolites and spatially promoting dopamine production and angiogenesis.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Dopamina , Humanos , Simulación del Acoplamiento Molecular , Dopamina/metabolismo , Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Metabolómica
9.
Mol Neurobiol ; 61(1): 74-90, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37581848

RESUMEN

There is clearly an unmet need for more effective and safer treatments for multiple sclerosis (MS). Our previous studies showed a significant therapeutic effect of matrine, a monomer of traditional herbal medicine, on experimental autoimmune encephalomyelitis (EAE) mice. To explore the mechanism of matrine action, we used 16S rRNA sequencing technology to determine the gut microbes in matrine-treated EAE mice and controls. The concentrations of short-chain fatty acids (SCFAs) were then tested by metabonomics. Finally, we established pseudo-sterile mice and transplanted into them fecal microbiota, which had been obtained from the high-dose matrine-treated EAE mice to test the effects of matrine. The results showed that matrine could restore the diversity of gut microbiota and promote the production of SCFAs in EAE mice. Transplantation of fecal microbiota from matrine-treated mice significantly alleviated EAE severity, reduced CNS inflammatory infiltration and demyelination, and decreased the level of IL-17 but increased IL-10 in sera of mice. In conclusion, matrine treatment can regulate gut microbiota and metabolites and halt the progression of MS.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Microbioma Gastrointestinal , Esclerosis Múltiple , Ratones , Animales , Microbioma Gastrointestinal/fisiología , Matrinas , ARN Ribosómico 16S/genética , Esclerosis Múltiple/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Ácidos Grasos Volátiles
10.
Food Chem ; 439: 138085, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38039612

RESUMEN

Chaenomeles speciosa (Sweet) Nakai fruit is a good source of phenolics with many health benefits. In this work, the enrichment of C. speciosa fruit total phenolics (CSFTP) using macroporous resins was studied. NKA-Ⅱ resin was selected for enriching CSFTP due to its highest adsorption/desorption quantity. Adsorption characteristics of CSFTP on NKA-Ⅱ resin exhibited a good fit with the Langmuir isotherm model and pseudo-second order kinetics model. This adsorption was spontaneous, exothermic, and entropy-decreasing through a physisorption mechanism. The breakthrough-elution curves were studied to optimize CSFTP enrichment conditions. One-step enrichment increased CSFTP content in the extracts from 26.51 % to 78.63 %, with a recovery of 81.03 %. A UPLC-QqQ-MS/MS method in multiple reaction monitoring (MRM) mode was established and validated for the simultaneous quantification of seven phenolic compounds. This study demonstrates the feasibility of industrial enrichment of CSFTP using NKA-Ⅱ resin and proposes a reliable method for quality control of CSFTP-rich products.


Asunto(s)
Extractos Vegetales , Rosaceae , Espectrometría de Masas en Tándem , Adsorción , Frutas , Cromatografía Líquida de Alta Presión/métodos , Fenoles , Resinas de Plantas
11.
Brain Res Bull ; 206: 110861, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38141789

RESUMEN

Based on the successful establishment of a rat model of chronic restraint stress, we used multiple algorithms to quantify the morphological changes of rat hypothalamic microglia from various perspectives, providing a pathomorphological basis for the subsequent study of molecular mechanisms of hypothalamic stress injury, such as neuroinflammation. To verify the successful establishment of the chronic stress model, an enzyme-linked immunosorbent assay was performed to detect serum glucocorticoid levels. Microglia labeled with Iba1 in frozen sections of rat hypothalamus were scanned and photographed at multiple levels using confocal microscopy. Subsequently, images were processed for external contouring and skeletonization, and morphological indices of microglia were calculated and analyzed using fractal, skeleton, and Sholl analysis. In addition, the co-expression of CD68 (a marker that can reflect phagocytic activity) and Iba1 was observed by immunofluorescence technique. Compared with the control group, microglia in the chronic stress group displayed reduced fractal dimension and lacunarity, increased density and circularity, enlarged soma areas, and shortened and reduced branches. Sholl analysis confirmed the reduced complexity of microglia following chronic stress. Meanwhile, microglia CD68 increased significantly, indicating that the microglia in the chronic stress group have greater phagocytosis activity. In summary, chronic restraint stress promoted the conversion of microglia in the rat hypothalamus to a less complex form, manifested as larger soma, shorter and fewer branches, more uniform and dense texture, and increased circularity; indeed, the shape of these microglia resembled that of amoeba and they displayed strong phagocytosis activity.


Asunto(s)
Hipotálamo , Microglía , Ratas , Animales
12.
Chemosphere ; 350: 141066, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38159731

RESUMEN

Radionuclide uranium is a great threat to human health, due to its high chemical toxicity and radioactivity. Finding suitable uranium decorporation to reduce damage caused by uranium internal contamination is an important aspect of nuclear emergency response. However, the poor selectivity and/or high toxicity of the only excretory promoter approved by Food and Drug Administration (FDA) is an obvious disadvantage. Herein, we choose an edible natural product, the traditional Chinese medicine called Perilla frutescens (PF), which has wide sources and can be used as an excellent and effective uranyl decorporation. In vivo uranium decorporation assays illustrate the removal efficiency of uranium in kidney were 68.87% and 43.26%, in femur were 56.66% and 54.53%, by the test of prophylactic and immediate administration, respectively. Cell level experiments confirmed that it had better biocompatibility than CaNa3-DTPA (CaNa3-diethylenetriamine pentaacetate, a commercial actinide excretion agent). In vitro static adsorption experiments exhibited that its excellent selectivity sorption for uranyl. All those results findings would provide new research insights about natural product for uranyl decorporation.


Asunto(s)
Productos Biológicos , Perilla frutescens , Uranio , Humanos , Uranio/toxicidad , Quelantes/farmacología , Riñón , Productos Biológicos/farmacología
13.
J Subst Use Addict Treat ; 156: 209189, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37866441

RESUMEN

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.


Asunto(s)
Depresión , Estimulación Magnética Transcraneal , Humanos , Ansiedad/terapia , Depresión/terapia , Conducta Impulsiva , Ritmo Teta/fisiología
14.
AAPS PharmSciTech ; 24(8): 247, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38030948

RESUMEN

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.


Asunto(s)
Povidona , Secado por Pulverización , Derivados de la Hipromelosa/química , Povidona/química , Medicina Tradicional , Tamaño de la Partícula
15.
PLoS One ; 18(10): e0286279, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37792689

RESUMEN

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI) is a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. In this survey study, we found that students who participated in the SCRI Program reported greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.


Asunto(s)
Investigación Biomédica , Neoplasias , Humanos , Investigación Biomédica/educación , Grupos Minoritarios/educación , Mentores , Hawaii , Recursos Humanos , Neoplasias/terapia
16.
Foods ; 12(16)2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37627999

RESUMEN

Type 2 diabetes mellitus (T2DM) has developed into an important health concern worldwide. The discovery of phlorotannins and their efficacy in the treatment of T2DM has become a hotspot for research in various fields. In this study, the potential phlorotannins and mechanism of six brown algae against T2DM were in-depth investigated using biological activity assays, LC-MS, and network pharmacology. First, the ethyl acetate fraction (EA frac.) showed high polyphenolic content and possessed significantly antioxidant and enzyme inhibitory abilities. Further, a total of fifty-nine peaks were obtained from six EA fracs. via UPLC-QE-MS/MS analysis, and fifteen of them were identified as phlorotannins and their isomers or derivatives. In detail, the chemical structures of six phlorotannins were inferred as dibenzodioxine-1,3,6,8-tetraol, bifuhalol, dioxinodehydroeckol, eckol, fucofurodiphlorethol, and fucotriphlorethol; three phlorotannin isomers were deduced to be fucophlorethol, trifucol, triphlorethol A, or triphlorethol B; and the phlorotannin derivative of m/z 263 was determined to be dibenzodioxine-1,2,3,6,8-pentanol or dibenzodioxine-1,2,4,5,7-pentanol. Moreover, 43 T2DM-related targets acted on by these chemicals were identified, and the function of phlorotannin to prevent and treat T2DM was elucidated in a holistic way based on the established compound-target-disease network, and GO function and KEGG pathway enrichment analysis.

17.
J Agric Food Chem ; 71(35): 13054-13065, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37619532

RESUMEN

One of the main reasons for consumer rejection of plant-based meat alternatives is the lack of meaty flavor after cooking. In this study, a platform was developed to generate meaty flavors solely from Allium substrates (chives, leeks, ramsons, and onions) using basidiomycete-mediated submerged fermentations. Polyporus umbellatus-mediated fermentation of onions resulted in an intense meaty and liver sausage-like flavor under proper fermentation parameters. Using multisolvent and solvent-free aroma extractions coupled with gas chromatography-mass spectrometry-olfactometry, 5 odorants with high assigned flavor dilution (FD) factors (≥ 256) were identified in the fermented sample that have been reported in the literature as important aroma compounds of meat products: methyl palmitate, bis(2-methyl-furyl) disulfide, (E,E)-2,4-decadienal, γ-nonalactone, and eugenol. Using selected ion monitoring, the presence of bis(2-methyl-furyl) disulfide (meaty, savory, FD 256) after fermentation was confirmed. It was proposed that P. umbellatus enzymatically forms bis(2-methyl-furyl) disulfide from intermediates derived from the thermal degradation of thiamine.


Asunto(s)
Odorantes , Cebollas , Fermentación , Carne , Disulfuros , Órganos de los Sentidos
18.
Sleep ; 46(10)2023 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-37531587

RESUMEN

STUDY OBJECTIVES: Healthy aging and many disorders show reduced sleep-dependent memory consolidation and corresponding alterations in non-rapid eye movement sleep oscillations. Yet sleep physiology remains a relatively neglected target for improving memory. We evaluated the effects of closed-loop auditory stimulation during sleep (CLASS) on slow oscillations (SOs), sleep spindles, and their coupling, all in relation to motor procedural memory consolidation. METHODS: Twenty healthy young adults had two afternoon naps: one with auditory stimulation during SO upstates and another with no stimulation. Twelve returned for a third nap with stimulation at variable times in relation to SO upstates. In all sessions, participants trained on the motor sequence task prior to napping and were tested afterward. RESULTS: Relative to epochs with no stimulation, upstate stimuli disrupted sleep and evoked SOs, spindles, and SO-coupled spindles. Stimuli that successfully evoked oscillations were delivered closer to the peak of the SO upstate and when spindle power was lower than stimuli that failed to evoke oscillations. Across conditions, participants showed similar significant post-nap performance improvement that correlated with the density of SO-coupled spindles. CONCLUSIONS: Despite its strong effects on sleep physiology, CLASS failed to enhance motor procedural memory. Our findings suggest methods to overcome this failure, including better sound calibration to preserve sleep continuity and the use of real-time predictive algorithms to more precisely target SO upstates and to avoid disrupting endogenous SO-coupled spindles and their mnemonic function. They motivate continued development of CLASS as an intervention to manipulate sleep oscillatory dynamics and improve memory.


Asunto(s)
Consolidación de la Memoria , Adulto Joven , Humanos , Estimulación Acústica , Consolidación de la Memoria/fisiología , Sueño/fisiología , Memoria/fisiología , Electroencefalografía
19.
medRxiv ; 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37292673

RESUMEN

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI), a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. This study assessed whether students who participated in the SCRI Program report greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

20.
Food Chem ; 426: 136617, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37336098

RESUMEN

Rapeseed oil, as one of the three major vegetable oils in the world, its matrix effect makes the decoding flavor a challenge. Solid-phase microextraction (SPME), SPME-Arrow, headspace stir bar sorptive extraction (HSSE), direct thermal desorption (DTD), and solvent-assisted flavor evaporation (SAFE) were compared based on the odorants in hot-pressed rapeseed oil. Besides, methodological validation for 31 aroma standards was conducted to compare reliability and robustness of these approaches. DTD showed the largest proportion of acids, while the other techniques extracted a majority of nitriles. The highest number of odorants was detected by SAFE (31), followed by HSSE (30), SPME-Arrow (30), SPME (24), and DTD (14). SPME-Arrow showed the best performance in linearity, recovery, and reproducibility followed by SPME, HSSE, DTD, and SAFE. Results reveal the advantages and limitations of diverse methodologies and provide valuable insights for the selection of extraction methods in an oil matrix and flavor decoding.


Asunto(s)
Odorantes , Compuestos Orgánicos Volátiles , Odorantes/análisis , Aceite de Brassica napus , Cromatografía de Gases y Espectrometría de Masas/métodos , Reproducibilidad de los Resultados , Microextracción en Fase Sólida/métodos , Solventes , Compuestos Orgánicos Volátiles/análisis
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