RESUMO
Myocardial infarction (MI) is an event of heart attack due to the formation of plaques in the interior walls of the arteries. This study is conducted to explore the role of ubiquitin-specific peptidase 47 (USP47) in cardiac function and inflammatory immunity. MI mouse models were established, followed by an appraisal of cardiac functions, infarct size, pathological changes, and USP47 and NLRP3 levels. MI cell models were established in HL-1 cells using anoxia. Levels of cardiac function-associated proteins, USP7, interferon regulatory factor 1 (IRF1), platelet factor-4 (CXCL4), pyroptotic factors, and neutrophil extracellular traps (NETs) were determined. The bindings of IRF1 to USP47 and the CXCL4 promoter and the ubiquitination of IRF1 were analyzed. USP47 was upregulated in myocardial tissues of MI mice. USP47 inhibition alleviated cardiac functions, and decreased infarct size, pro-inflammatory cytokines, NETs, NLRP3, and pyroptosis. The ubiquitination and expression levels of IRF1 were increased by silencing USP47, and IRF1 bound to the CXCL4 promoter to promote CXCL4. Overexpression of IRF1 or CXCL4 in vitro and injection of Nigericin in vivo reversed the effect of silencing USP47 on alleviating pyroptosis and cardiac functions. Collectively, USP47 stabilized IRF1 and promoted CXCL4, further promoting pyroptosis, impairing cardiac functions, and aggravating immune inflammation through NLRP3 pathways.
Assuntos
Inflamassomos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/metabolismo , Camundongos , Inflamassomos/metabolismo , Masculino , Piroptose , Fator Regulador 1 de Interferon/metabolismo , Fator Regulador 1 de Interferon/genética , Modelos Animais de Doenças , Linhagem Celular , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Fator Plaquetário 4/metabolismo , Fator Plaquetário 4/genética , Ubiquitinação , HumanosRESUMO
BACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.
Assuntos
Ácido Araquidônico , Microbioma Gastrointestinal , Radioisótopos do Iodo , Protetores contra Radiação , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos da radiação , Radioisótopos do Iodo/efeitos adversos , Camundongos , Protetores contra Radiação/farmacologia , Humanos , Ácido Araquidônico/metabolismo , Masculino , Feminino , Adulto , Neoplasias da Glândula Tireoide/radioterapia , Pessoa de Meia-Idade , Suplementos Nutricionais , Irradiação Corporal Total/efeitos adversosRESUMO
Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.
RESUMO
This work presents a resilient distributed optimization algorithm based on the event-triggering mechanism for cyber-physical systems (CPSs) to optimize an average of convex cost functions corresponding to multiple agents under adversarial environments. Two attack scenarios, including the f-total (each agent is affected by at most f malicious agents in the whole network) and the f-local (each agent is affected by at most f malicious agents in its in-neighbor set) attacks are considered. Subsequently, the convergence conditions under these two attack scenarios are provided, respectively, both of which guarantee that the state values of benign agents converge to a bounded error range. The optimality conditions are also presented by theoretical analysis, which guarantee that the state values of benign agents converge to a safety interval constructed by local optimal values under certain graph conditions, despite the misbehavior of malicious agents. In addition, four numerical examples are presented to show the effectiveness and superiority of the event-triggering resilient distributed optimization (RDO-E) algorithm. Compared to existing resilient algorithms, the proposed method achieves resilient distributed optimization with higher accuracy and less demanding communication overheads. Finally, by applying the proposed method to the multi-microgrid system, a resilient economic dispatch problem (REDP) is successfully solved, which validates the practical viability of the RDO-E algorithm.
RESUMO
Acidic pit lakes (APLs) emerge as reservoirs of acid mine drainage in flooded open-pit mines, representing extreme ecosystems and environmental challenges worldwide. The bioremediation of these oligotrophic waters necessitates the addition of organic matter, but the biogeochemical response of APLs to exogenous organic matter remains inadequately comprehended. This study delves into the biogeochemical impacts and remediation effects of digestate-derived organic matter within an APL, employing a multi-omics approach encompassing geochemical analyses, amplicon and metagenome sequencing, and ultra-high resolution mass spectrometry. The results indicated that digestate addition first stimulated fungal proliferation, particularly Ascomycetes and Basidiomycetes, which generated organic acids through lignocellulosic hydrolysis and fermentation. These simple compounds further supported heterotrophic growth, including Acidiphilium, Acidithrix, and Clostridium, thereby facilitating nitrate, iron, and sulfate reduction linked with acidity consumption. Nutrients derived from digestate also promoted the macroscopic development of acidophilic algae. Notably, the increased sulfate reduction-related genes primarily originated from assimilatory metabolism, thus connecting sulfate decrease to organosulfur increase. Assimilatory and dissimilatory sulfate reduction collectively contributed to sulfate removal and metal fixation. These findings yield multi-omics insights into APL biogeochemical responses to organic matter addition, enhancing the understanding of carbon-centered biogeochemical cycling in extreme ecosystems and guiding organic amendment-based bioremediation in oligotrophic polluted environments.
Assuntos
Ecossistema , Lagos , Lagos/química , Biodegradação Ambiental , Multiômica , Ácidos , Sulfatos/metabolismoRESUMO
For some engineering application, accurately estimating reliability only depend on the history data or failure mechanism is difficult to implement, due to the lack of data and imperfect theory of failure mechanism. Namely, both history data and failure mechanism should be utilized to improve the reliability estimation accuracy for engineering applications. Hence, we construct a reliability estimation method by fusing the failure mechanism and artificial neural network (ANN) supported Wiener processes for utilizing both history data and failure mechanism. ANN and failure mechanism are integrated into Wiener process with random effects, respectively. Bayesian model averaging (BMA) method is adapted to combine the failure mechanism with ANN supported Wiener processes, as well as to update the model parameters by fusing data. Based on a typical aviation hydraulic pump's actual dataset, we illustrate the advantages of our approach by comparing to Wiener process supported only by ANN or failure mechanism in engineering practices. The proposed method shows superiorities on reliability estimation considering the estimation accuracies comparing the other two models.
RESUMO
Ophiopogonis Radix (OR) is a traditional Chinese medicine. In recent years, in order to achieve the purpose of drying, bleaching, sterilizing and being antiseptic, improving appearance, and easy storage, people often use sulfur fumigation for its processing. However, changes in the chemical composition of medicinal herbs caused by sulfur fumigation can lead to the transformation and loss of potent substances. Therefore, the development of methods to rapidly reveal the chemical transformation of medicinal herbs induced by sulfur fumigation can guarantee the safe clinical use of medicines. In this study, a combined full scan-parent ions list-dynamic exclusion acquisition-diagnostic product ions analysis strategy based on UHPLC-LTQ-Orbitrap MS was proposed for the analysis of steroidal saponins and their transformed components in sulfur-fumigated Ophiopogonis Radix (SF-OR). Based on precise mass measurements, chromatographic behavior, neutral loss ions, and diagnostic product ions, 286 constituents were screened and identified from SF-OR, including 191 steroidal saponins and 95 sulfur-containing derivatives (sulfates or sulfites). The results indicated that the established strategy was a valuable and effective analytical tool for comprehensively characterizing the material basis of SF-OR, and also provided a basis for potential chemical changes in other sulfur-fumigated herbs.
Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Saponinas , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Enxofre/química , Plantas Medicinais/química , Fumigação/métodos , SulfitosRESUMO
Under natural physiological conditions, anthocyanins can keep bright and stable color for a long time due to the relatively stable acid-base environment of plant vacuoles and the copigmentation from various copigment substances, such as polyphenols, nucleotides, metallic ions and other substances. Therefore, the copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale yellow organic molecules (copigments). These interactions are usually manifested in both hyperchromic effect and bathochromic shifts. In addition to making anthocyanins more stable, the copigmentation also could make an important contribution to the diversification of their tone. Based on the molecular structure of anthocyanins, this review focuses on the interaction mode of auxochrome groups or copigments with anthocyanins and their effects on the chemical and color stability of anthocyanins.
Assuntos
Antocianinas , Polifenóis , Antocianinas/química , Estrutura Molecular , ÍonsRESUMO
This article presents a novel approach to leverage generative adversarial networks(GANs) techniques to learn a feedback linearization controller(FLC) for a class of uncertain nonlinear systems. By estimating uncertainty through the adversarial process, where ground truth samples are exclusively obtained from a predefined integral model, the feedback linearization controller, learned through a minimax two-player optimization framework, enhances the reference tracking performance of the input-output uncertain nonlinear system. Furthermore, we provide theoretical guarantee of convergence and stability, demonstrating the safe recovery of robust FLC. We also address the common challenge of mode collapse in GANs training through the strict convexity of our synthesized generator structure and an enhanced adversarial loss. Comprehensive simulations and practical experiments are conducted to underscore the superiority and efficacy of our proposed approach.
RESUMO
Objective: The objective of this experiment was to investigate the relationship between the circadian rhythm of blood pressure and left ventricular hypertrophy (LVH) in patients with hypertension. Methods: A total of 500 hypertension patients with documented circadian rhythm of blood pressure were selected for this study. The researchers collected general patient data and fasting blood samples. The following parameters were measured within subgroups of hypertensive patients: age, sex ratio, BMI, fasting blood glucose, total cholesterol, triacylglycerol, HDL-C, LDL-C, duration of hypertension, antihypertensive drug usage, and statin intake. Results: The results of the study showed that LVH hypertension had a significantly higher proportion of grade 3 hypertension compared to non-LVH hypertension (P < .001). Additionally, LVH hypertension displayed higher mean systolic blood pressure levels over a 24-hour period (P = .002), during daytime (P = .029), and during nighttime (P < .001). The 24-hour pulse pressure (P < .001) and pulse pressure index (P = 0.001) were also significantly higher in patients with LVH hypertension. Furthermore, the rate of blood pressure decline at night was significantly lower in the LVH hypertension group compared to the control group (P < .001). B-type natriuretic peptide (BNP) levels (P = .034) and left ventricular mass index (LVMI) (P < .001) were significantly higher in patients with LVH hypertension compared to non-LVH patients. Conclusions: The findings of this study suggest a close association between hypertensive LVH and the weakening or disappearance of the circadian rhythm of blood pressure. It was also observed that the level of blood pressure classification and plasma BNP levels were increased in patients with LVH hypertension.
Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Humanos , Pressão Sanguínea , Hipertensão/complicações , Anti-Hipertensivos/uso terapêutico , Ritmo CircadianoRESUMO
BACKGROUND: Appropriate time for ejection fraction (EF) reassessment after revascularization in patients with left ventricular dysfunction has not been investigated comprehensively, although 3 months after revascularization is recommended to stratify the risk of sudden cardiac death (SCD). HYPOTHESIS: EF reassessed within different timeframe after revascularization may have incosistent contribution for risk stratification of SCD. METHODS: Patients who had EF ≤ 40% before revascularization and had EF reassessment at least once during follow-up were included. The role of early (<3 months) versus late (3-12 months) EF measurements in prediction of all-cause mortality and SCD were compared. RESULTS: A total of 1589 patients were identified. EF reassessed <3 months was lower than EF reassessed within 3-12 months (42.1 ± 9.7% vs. 45.8 ± 10.8%; p < .01). Among 1069 patients who had EF reassessed <3 months, EF ≤ 35% was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.22-2.29; p < .01), but had no association with the risk of SCD (HR, 1.44; 95% CI, 0.84-2.48; p = .18). By contrast, among 595 patients who had EF reassessed within 3-12 months, EF ≤ 35% was associated with higher risks of both all-cause death (HR, 1.81; 95% CI, 1.06-3.10; p = .03) and SCD (HR, 2.71; 95% CI, 1.31-5.61; p < .01). The relative contribution of SCD to all-cause death was higher in patients with EF ≤ 35% than patients with EF > 35% when EF was reassessed within 3-12 months (p = .04). However, when EF was reassessed <3 months, the mode of death was similar in patients with EF ≤ 35% versus >35% (p = .85). CONCLUSIONS: 3 to 12 months after revascularization may be appropriate for cardiac function reassessment and SCD risk stratification.
Assuntos
Desfibriladores Implantáveis , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico , Fatores de Risco , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Medição de Risco , Desfibriladores Implantáveis/efeitos adversosRESUMO
Hierarchical frameworks-a special class of directed frameworks with a layer-by-layer architecture-can be an effective mechanism to coordinate robot swarms. Their effectiveness was recently demonstrated by the mergeable nervous systems paradigm (Mathews et al., 2017), in which a robot swarm can switch dynamically between distributed and centralized control depending on the task, using self-organized hierarchical frameworks. New theoretical foundations are required to use this paradigm for formation control of large swarms. In particular, the systematic and mathematically analyzable organization and reorganization of hierarchical frameworks in a robot swarm is still an open problem. Although methods for framework construction and formation maintenance via rigidity theory exist in the literature, they do not address cases of hierarchy in a robot swarm. In this article, we extend bearing rigidity to directed topologies and extend the Henneberg constructions to generate self-organized hierarchical frameworks with bearing rigidity. We investigate three-key self-reconfiguration problems: 1) framework merging; 2) robot departure; and 3) framework splitting. We also derive the mathematical conditions of these problems and then develop algorithms that preserve rigidity and hierarchy using only local information. Our approach can be used for formation control generally, as in principle it can be coupled with any control law that makes use of bearing rigidity. To demonstrate and validate our proposed hierarchical frameworks and methods, we apply them to four scenarios of reactive formation control using an example control law.
RESUMO
Eupolyphaga sinensis Walker (ESW) is a traditional Chinese medicine formulation used to treat hyperlipidemia. However, the hypolipidemic effect of the active peptides from E. sinensis Walker (APE) is incompletely understood. We studied the hypolipidemic effect of APE and explored the impact of APE on the gut microbiota (GM) in rats suffering from hyperlipidemia. APE was prepared by enzymatic digestion, and its structure was characterized using various methods. The anti-hyperlipidemic activity of APE was assessed using a high-fat diet (HFD)-induced model in zebrafish and rats. In rats, HFD administration caused abnormalities of lipid metabolism and disturbances of the GM and amino acid (AA) profile in plasma. The abundance of bacteria of the phyla Firmicutes and Bacteroides was increased significantly (p < 0.05), and the relative abundance of Lactobacillus species and Clostridium species was decreased significantly (p < 0.05). HFD therapy affected the levels of 12 AAs in vivo: 10 AAs showed increased levels and two AAs had decreased levels (p < 0.05). Similar results were demonstrated in an experiment on fecal microbiota transplantation. APE treatment dose-dependently decreased lipid factors and liver damage (p < 0.05). Sequencing of the 16 S rRNA gene indicated that APE improved the intestinal-flora structure of rats with HL markedly, and increased the relative abundance of Lactobacillus species and Clostridium species. Metabolomics analysis indicated that APE could alter the levels of 10 AAs affected by HFD consumption. Spearman correlation analysis revealed that gamma-aminobutyric acid (GABA) could be a crucial metabolite, and Lactobacillus species and Clostridium species might be important bacteria for the action of APE against hyperlipidemia. We speculate that APE exhibited an anti-hyperlipidemic effect by regulating GABA synthesis in the presence of Lactobacillus species and Clostridium species.
Assuntos
Microbioma Gastrointestinal , Hominidae , Hiperlipidemias , Ratos , Animais , Hiperlipidemias/metabolismo , Peixe-Zebra , Dieta Hiperlipídica/efeitos adversos , Biomarcadores , Lactobacillus , Bactérias , Ácido gama-Aminobutírico/farmacologiaRESUMO
Astragalosides (AGs), as one of the main active ingredients in Astragali Radix (AR), have a series of biological activities. Previous studies have only qualitatively identified the metabolites of AGs in AR, resulting in a lack of quantification. In the present study, the original material was selected from 12 origins based on the levels of 4 AGs by high-performance liquid chromatography (HPLC). The prototype components and metabolites of total AGs (TAGs) in feces, urine, and plasma samples of rats were thoroughly screened and characterized by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). The fermentation reaction and metabolites were verified by human fecal TAG fermentation in vitro. The metabolites of AG I, II, and IV transformed by human feces at different times were identified using UHPLC-HRMS, and the partial metabolites were quantified by HPLC. Furthermore, the anti-inflammatory and antioxidant activities of the metabolites were evaluated based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells in vitro. In total, 13 AGs and 170 metabolites were identified in TAGs as well as in the plasma, urine, and feces of Sprague-Dawley (SD) rats by UHPLC-HRMS, including 28, 36, and 170 metabolites in the plasma, urine, and feces, respectively. The metabolites included the products of deglycosylation, demethylation, hydroxylation, glucuronidation, sulfation, and cysteine-binding reactions. Moreover, the TAG fermentation results in vitro showed great similarity. The human fecal incubation experiments for AG I, II, and IV demonstrated that the metabolic reaction of TAGs mainly occurred in intestinal feces and that deglycosylation, demethylation, and hydroxylation were the main pathways of their metabolism. HPLC quantitative analysis of the transformation solution at different time points showed that AGs were transformed into secondary glycosides [cycloastragenol-6-glucoside (CAG-6-glucoside)] and aglycones [cycloastragenol (CAG)] through a deglycosylation reaction. Analysis of the pharmacological activity showed that the anti-inflammatory and antioxidant activities of the metabolites were associated with the levels of the corresponding aglycones. Further, metabolic profiles of the TAGs were constructed. Overall, this study revealed the metabolic process of AGs in the intestine, providing guidance for the metabolism and pharmacological effects of other saponins.
Assuntos
Astrágalo , Medicamentos de Ervas Chinesas , Ratos , Humanos , Animais , Ratos Sprague-Dawley , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Biotransformação , Glucosídeos , Anti-InflamatóriosRESUMO
The controller is important for the artificial pancreas to guide insulin infusion in diabetic therapy. However, the inter- and intra-individual variability and time delay of glucose metabolism bring challenges to control glucose within a normal range. In this study, a multivariable identification based model predictive control (mi-MPC) is developed to overcome the above challenges. Firstly, an integrated glucose-insulin model is established to describe insulin absorption, glucose-insulin interaction under meal disturbance, and glucose transport. On this basis, an observable glucose-insulin dynamic model is formed, in which the individual parameters and disturbances can be identified by designing a particle filtering estimator. Next, embedded with the identified glucose-insulin dynamic model, a mi-MPC method is proposed. In this controller, plasma glucose concentration (PGC), an important variable and indicator of glucose regulation, is estimated and controlled directly. Finally, the method was tested on 30 in-silico subjects produced by the UVa/Padova simulator. The results show that the mi-MPC method including the model, individual identification, and the controller can regulate glucose with the mean value of 7.45 mmol/L without meal announcement.
RESUMO
The active peptide (APE) of Eupolyphaga sinensis Walker, which is prepared by bioenzymatic digestion, has significant antihyperlipidemic effects in vivo, but its mechanism of action on hyperlipidemia is not clear. Recent studies on amino acid metabolism suggested a possible link between it and hyperlipidemia. In this study, we first characterized the composition of APE using various methods. Then, the therapeutic effects of APE on hyperlipidemic rats were evaluated, including lipid levels, the inflammatory response, and oxidative stress. Finally, the metabolism-regulating mechanisms of APE on hyperlipidemic rats were analyzed using untargeted and targeted metabolomic approaches. The results showed that APE significantly reduced the accumulation of fat, oxidative stress levels, and serum pro-inflammatory cytokine levels. Untargeted metabolomic analysis showed that the mechanism of the hypolipidemic effect of APE was mainly related to tryptophan metabolism, phenylalanine metabolism, arginine biosynthesis, and purine metabolism. Amino-acid-targeted metabolomic analysis showed that significant differences in the levels of eight amino acids occurred after APE treatment. Among them, the expression of tryptophan, alanine, glutamate, threonine, valine, and phenylalanine was upregulated, and that of arginine and proline was downregulated in APE-treated rats. In addition, APE significantly downregulated the mRNA expression of SREBP-1, SREBP-2, and HMGCR. Taking these points together, we hypothesize that APE ameliorates hyperlipidemia by modulating amino acid metabolism in the metabolome of the serum and feces, mediating the SREBP/HMGCR signaling pathway, and reducing oxidative stress and inflammation levels.
Assuntos
Hominidae , Hiperlipidemias , Doenças Metabólicas , Ratos , Animais , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1 , Triptofano/uso terapêutico , Metabolômica , Peptídeos/uso terapêutico , Arginina/uso terapêutico , Fenilalanina/uso terapêuticoRESUMO
Genipin, an aglycone of geniposide, is a rich iridoid component in the fruit of Gardenia jasminoides Ellis and has numerous biological activities. However, its metabolic profiles in vivo and vitro remain unclear. In this study, an effective analytical strategy based on ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) in positive and negative ion modes was developed to analyze and identify genipin metabolites in rat urine, blood, feces, and fecal fermentation in combination with many methods including post-collection data mining methods, high-resolution extracted ion chromatography (HREIC), and multiple mass defect filtering (MMDF). Simultaneously, the metabolites of genipin in vivo were verified by fecal fermentation of SD rats at different times. Finally, based on information such as reference substances, chromatographic retention behavior, and accurate mass determination, a total of 50 metabolites (including prototypes) were identified in vivo. Among them, 7, 31 and 28 metabolites in vivo were identified in blood, urine, and feces, respectively. Our results showed that genipin could generate different metabolites that underwent multiple metabolic reactions in vivo including methylation, hydroxylation, dehydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and their superimposed reactions. Forty-six metabolites were verified in vitro. Meanwhile, 2 and 19 metabolites identified in blood and urine were also verified in fecal fermentation at different times. These results demonstrated that metabolites were produced in feces and reabsorbed into the body. In conclusion, the newly discovered metabolites of genipin can provide a new perspective for understanding its pharmacological effects and build the foundation for thee toxicity and safety evaluations of genipin.
Assuntos
Iridoides , Animais , Ratos , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão , Espectrometria de MassasRESUMO
Acidic pit lakes represent hydrological features resulting from the accumulation of acid mine drainage in mining operations. Long-term monitoring is essential for these extreme and contaminated environments, yet tracking investigations integrating microbial geochemical dynamics in acidic pit lakes have been lacking thus far. This study integrated historical data with field sampling to track decadal biogeochemical changes in an acidic pit lake. With limited artificial disturbance, significant and sustained biogeochemical changes were observed over the past decade. Surface water pH slowly increased from 2.8 to a maximum of 3.6, with a corresponding increase in bottom water pH to around 3.9, despite the accumulation of externally imported sulfate and metals. Elevated nutrient levels stimulated the macroscopic growth of Chlorophyta, resulting in a shift from reddish-brown to green water with floating algal bodies. Furthermore, microalgae-fixed organic carbon promoted the transition from the initial chemolithotrophy-based population dominated by Acidiphilium and Ferrovum to a heterotrophic community. The increase in heterotrophic iron- and sulfate-reducers may cause an elevation in ferrous levels and a decline in copper concentrations. However, most metals were not removed from the water column, potentially due to insufficient biosulfidogenesis or sulfide reoxidation. These findings offer novel insights into microbial succession in extreme ecosystem evolution and contribute to the management and remediation of acidic pit lakes.
Assuntos
Lagos , Microbiota , Metais , Sulfatos , ÁguaRESUMO
Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (< 0.04%, w/w) severely limits its application. The purpose of this study is to improve the biotransformation of AG IV and its bioaccessibility during in vitro digestion by Poria cocos solid fermenting Radix Astragali. The optimum fermentation conditions were as follows: Inoculation amount 8 mL; fermentation time 10 d; fermentation humidity 90%. Through fermentation, the content of AG IV was increased from 384.73 to 1986.49 µg/g by 5.16-fold. After in vitro digestion, the contents of genistin, calycosin, formononetin, AG IV, Astragaloside II (AG II) and total flavonoids in fermented Radix Astragali (FRA) of enteric phase II (ENTII) were 34.52 µg/g, 207.32 µg/g, 56.76 µg/g, 2331.46 µg/g, 788.31 µg/g, 3.37 mg/g, which were 2.08-fold, 2.51-fold, 1.05-fold, 8.62-fold, 3.22-fold and 1.50-fold higher than those of control, respectively. The Scanning electron microscopy (SEM) of FRA showed rough surface and porous structure. The DPPH and ABTS radical scavenging rate of FRA were higher than those of control. These results showed that the Poria cocos solid fermentation could increase the content of the AG IV in Radix Astragali and improve the bioaccessibility and antioxidant activity of Radix Astragali, which is providing new ideas for future development and utilization of Radix Astragali.
Assuntos
Medicamentos de Ervas Chinesas , Wolfiporia , Antioxidantes , Fermentação , Medicamentos de Ervas Chinesas/química , Biotransformação , Digestão , Cromatografia Líquida de Alta Pressão/métodosRESUMO
The stratified acidic pit lake formed by the confluence of acid mine drainage has a unique ecological niche and is a model system for extreme microbial studies. Eukaryotes are a component of the AMD community, with the main members including microalgae, fungi, and a small number of protozoa. In this study, we analyzed the structural traits and interactions of eukaryotes (primarily fungi and microalgae) in acidic pit lakes subjected to environmental gradients. Based on the findings, microalgae and fungi were found to dominate different water layers. Specifically, Chlorophyta showed dominance in the well-lit aerobic surface layer, whereas Basidiomycota was more abundant in the dark anoxic lower layer. Co-occurrence network analysis showed that reciprocal relationships between fungi and microalgae were prevalent in extremely acidic environments. Highly connected taxa within this network were Chlamydomonadaceae, Sporidiobolaceae, Filobasidiaceae, and unclassified Eukaryotes. Redundancy analysis (RDA) and random forest models revealed that Chlorophyta and Basidiomycota responded strongly to environmental gradients. Further analysis indicated that eukaryotic community structure was mainly determined by nutrient and metal concentrations. This study investigates the potential symbiosis between fungi and microalgae in the acidic pit lake, providing valuable insights for future eukaryotic biodiversity studies on AMD remediation.