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2.
Transgenic Res ; 33(1-2): 59-66, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38564120

RESUMO

Several expression systems have been developed in clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) framework allowing for gene editing of disease-associated genes across diverse citrus varieties. In this study, we present a new approach employing a multi-intron containing Cas9 gene plus multiple gRNAs separated with tRNA sequences to target the phytoene desaturase gene in both 'Carrizo' citrange and 'Duncan' grapefruit. Notably, using this unified vector significantly boosted editing efficiency in both citrus varieties, showcasing mutations in all three designated targets. The implementation of this multiplex gene editing system with a multi-intron-containing Cas9 plus a gRNA-tRNA array demonstrates a promising avenue for efficient citrus genome editing, equipping us with potent tools in the ongoing battle against several diseases such as canker and huanglongbing.


Assuntos
Citrus , Edição de Genes , Sistemas CRISPR-Cas/genética , Íntrons , Citrus/genética , RNA Guia de Sistemas CRISPR-Cas , RNA de Transferência/genética
3.
Environ Sci Pollut Res Int ; 30(55): 117759-117771, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37874514

RESUMO

Green innovation is an important driving force for high-quality development and is vital for reinvigorating the old industrial bases in Northeast China. As such, this study investigates the spatial-temporal evolution characteristics and factors influencing green innovation efficiency (GIE) in Northeast China from 2005 to 2020, using the super-efficient EBM-Malmquist model, kernel density estimation, and random forest model. The results show the following. (1) The "growth effect" of technological change is the main force driving GIE improvement; the "horizontal effect" of pure technical efficiency change has started to play an important role; and the club convergence characteristics of GIE in Northeast China have started to be optimized. (2) GIE in Northeast China shows significant spatial differentiation. The urban agglomeration of Mid-southern Liaoning and Harbin-Changchun has had high values for GIE, indicating that green innovation has a cyclic cumulative effect and the spatial pattern of green innovation needs to be further optimized. (3) The random forest model is more accurate and provides more trustworthy results compared with the traditional multiple linear regression model. The results of random forest model measurement illustrate that the number of digital economy enterprises, public finance expenditure, GDP per capita, and vegetation coverage play a positive role in promoting GIE. The proportion of the non-farm population and industrial agglomeration plays a negative role in GIE. In the same period, the contribution of the number of digital economy enterprises≥0.41, public expenditure ≥0.47, GDP per capita≥0.39, and vegetation coverage≥0.36 to GIE reach maximum values and then remain unchanged.


Assuntos
Cabeça , Gastos em Saúde , China , Indústrias , Modelos Lineares , Desenvolvimento Econômico , Eficiência
4.
Nat Commun ; 14(1): 6848, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891163

RESUMO

Systemic acquired resistance (SAR) is a long-lasting broad-spectrum plant defense mechanism induced in distal systemic tissues by mobile signals generated at the primary infection site. Despite the discoveries of multiple potential mobile signals, how these signals cooperate to trigger downstream SAR signaling is unknown. Here, we show that endogenous extracellular nicotinamide adenine dinucleotide (phosphate) [eNAD(P)] accumulates systemically upon pathogen infection and that both eNAD(P) and the lectin receptor kinase (LecRK), LecRK-VI.2, are required in systemic tissues for the establishment of SAR. Moreover, putative mobile signals, e.g., N-hydroxypipecolic acid (NHP), trigger de novo systemic eNAD(P) accumulation largely through the respiratory burst oxidase homolog RBOHF-produced reactive oxygen species (ROS). Importantly, NHP-induced systemic immunity mainly depends on ROS, eNAD(P), LecRK-VI.2, and BAK1, indicating that NHP induces SAR primarily through the ROS-eNAD(P)-LecRK-VI.2/BAK1 signaling pathway. Our results suggest that mobile signals converge on eNAD(P) in systemic tissues to trigger SAR through LecRK-VI.2.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , NAD/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças das Plantas , Regulação da Expressão Gênica de Plantas
5.
Sci Total Environ ; 896: 165232, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37392892

RESUMO

Arsenic (As) is a toxic metalloid, elevated levels of which in soils are becoming a major global environmental issue that poses potential health risks to humans. Pteris vittata, the first known As hyperaccumulator, has been successfully used to remediate As-polluted soils. Understanding why and how P. vittata hyperaccumulates As is the core theoretical basis of As phytoremediation technology. In this review, we highlight the beneficial effects of As in P. vittata, including growth promotion, elemental defense, and other potential benefits. The stimulated growth of P. vittata induced by As can be defined as As hormesis, but differs from that in non-hyperaccumulators in some aspects. Furthermore, the As coping mechanisms of P. vittata, including As uptake, reduction, efflux, translocation, and sequestration/detoxification are discussed. We hypothesize that P. vittata has evolved strong As uptake and translocation capacities to obtain beneficial effects from As, which gradually leads to As accumulation. During this process, P. vittata has developed a strong As vacuolar sequestration ability to detoxify overloaded As, which enables it to accumulate extremely high As concentrations in its fronds. This review also provides insights into several important research gaps that need to be addressed to advance our understanding of As hyperaccumulation in P. vittata from the perspective of the benefits of As.


Assuntos
Arsênio , Pteris , Poluentes do Solo , Humanos , Arsênio/análise , Pteris/metabolismo , Poluentes do Solo/análise , Biodegradação Ambiental , Solo , Raízes de Plantas/metabolismo
6.
Plants (Basel) ; 12(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37111879

RESUMO

The ability of plants to accumulate heavy metals is a crucial factor in phytoremediation. This study investigated the effect of NaCl and S,S-ethylenediaminesuccinic acid (EDDS) on heavy metal accumulation in Kosteletzkya pentacarpos in soil polluted with arsenic, cadmium, lead, and zinc. The addition of NaCl reduced the bioavailability of arsenic and cadmium, while EDDS increased the bioavailability of arsenic and zinc. The toxicity of the polymetallic pollutants inhibited plant growth and reproduction, but NaCl and EDDS had no significant positive effects. NaCl reduced the accumulation of all heavy metals in the roots, except for arsenic. In contrast, EDDS increased the accumulation of all heavy metals. NaCl reduced the accumulation of arsenic in both the main stem (MS) and lateral branch (LB), along with a decrease in cadmium in the leaves of the main stem (LMS) and zinc in the leaves of the lateral branch (LLB). Conversely, EDDS increased the accumulation of all four heavy metals in the LB, along with an increase in arsenic and cadmium in the LMS and LLB. Salinity significantly decreased the bioaccumulation factor (BF) of all four heavy metals, while EDDS significantly increased it. NaCl had different effects on heavy metals in terms of the translocation factor (TFc), increasing it for cadmium and decreasing it for arsenic and lead, with or without EDDS. EDDS reduced the accumulation of all heavy metals, except for zinc, in the presence of NaCl in polluted soil. The polymetallic pollutants also modified the cell wall constituents. NaCl increased the cellulose content in the MS and LB, whereas EDDS had little impact. In conclusion, salinity and EDDS have different effects on heavy metal bioaccumulation in K. pentacarpos, and this species has the potential to be a candidate for phytoremediation in saline environments.

7.
J Exp Bot ; 74(9): 2891-2911, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-36723875

RESUMO

Climate change has intensified the infection of tomato plants by pathogens such as Pseudomonas syringae pv. tomato (Pst). Rootstocks may increase plant tolerance to leaf phytopathogens. The aim of this study was to evaluate the effects of the tolerant Poncho Negro (R) tomato rootstock on physiological defence and the role of hydrogen sulfide (H2S) in susceptible Limachino (L) tomato plant responses to Pst attack. Ungrafted (L), self-grafted (L/L), and grafted (L/R) plants were infected with Pst. Rootstock increased the concentration of antioxidant compounds including ascorbate in the scion. Tolerant rootstock induced an increase of H2S in the scion, which correlated with enhanced expression of the SlAPX2 gene. A high accumulation of salicylic acid was observed in Pst-inoculated grafted L/L and L/R plants, but this was higher in L/R plants. The increase of H2S during Pst infection was associated with a reduction of ethylene in L/R plants. Our study indicates that the Poncho Negro rootstock reduced the symptoms of bacterial speck disease in the Limachino tomato plants, conferring tolerance to Pst infection. This study provides new knowledge about the impact of rootstock in the defence of tomato plants against leaf pathogens that could be used in sustainable management of tomato cultivation.


Assuntos
Pseudomonas syringae , Solanum lycopersicum , Solanum lycopersicum/genética , Plantas , Folhas de Planta/fisiologia , Doenças das Plantas/microbiologia
8.
Bull Environ Contam Toxicol ; 110(1): 12, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36512146

RESUMO

The widespread occurrence of cyanobacteria blooms damages the water ecosystem and threatens the safety of potable water and human health. Exogenous L-lysine significantly inhibits the growth of a dominant cyanobacteria Microcystis aeruginosa in freshwater. However, the molecular mechanism of how lysine inhibits the growth of M. aeruginosa is unclear. In this study, both non-target and target metabolomic analysis were performed to investigate the effects of algicide L-lysine. The results showed that 8 mg L- 1 lysine most likely disrupts the metabolism of amino acids, especially the arginine and proline metabolism. According to targeted amino acid metabolomics analysis, only 3 amino acids (L-arginine, ornithine, and citrulline), which belong to the ornithine-ammonia cycle (OAC) in arginine metabolic pathway, showed elevated levels. The intracellular concentrations of ornithine, citrulline, and arginine increased by 115%, 124%, and 19.4%, respectively. These results indicate that L-lysine may affect arginine metabolism and OAC to inhibit the growth of M. aeruginosa.


Assuntos
Cianobactérias , Herbicidas , Microcystis , Humanos , Microcystis/metabolismo , Lisina/toxicidade , Lisina/metabolismo , Citrulina/metabolismo , Ecossistema , Herbicidas/metabolismo , Cianobactérias/metabolismo , Ornitina/toxicidade , Ornitina/metabolismo , Arginina/química , Arginina/metabolismo , Amônia , Microcistinas/metabolismo
9.
Org Biomol Chem ; 20(48): 9613-9617, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36420677

RESUMO

A metal-free tandem reduction and N-trifluoroethylation of quinolines and quinoxalines has been developed. It provided a convenient route to access trifluoroethylated tetrahydroquinolines and tetrahydroquinoxalines. This one-pot method avoids the purification process of the intermediate. Mechanistically, the in situ-generated boryl acetal species reacted with tetrahydroquinolines to generate iminiums followed by reduction to give the target compounds.


Assuntos
Boranos , Quinolinas , Quinoxalinas , Ácido Trifluoracético
10.
Org Lett ; 24(40): 7440-7445, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36173131

RESUMO

The metal-free reductive N-trifluoroethylation and N-trifluoroacetylation of indoles have been developed. Bench stable and inexpensive trimethylamine borane and trifluoroacetic acid (TFA) were utilized as the reductive and fluorinating reagents, respectively. These transformations were switchable on the basis of altering the loading of trimethylamine borane and TFA. Preliminary experiments indicated indoline was the common intermediate in these two transformations.


Assuntos
Boranos , Indóis , Metilaminas , Ácido Trifluoracético
11.
Int Immunopharmacol ; 111: 109084, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35932613

RESUMO

BACKGROUNDS: Drug induced liver injury (DILI) is sometimes similar to autoimmune hepatitis (AIH) in serology and histology. Clinicians empirically screened DILI with significant autoimmune characteristics to implement clinical intervention. We tried to characterize DILI with autoantibodies by metabolomics. METHODS: Untargeted metabolomics coupled with pattern recognition approaches were performed on sera samples including AIH (n = 59), DILI with autoantibodies (DILIAb+, n = 68), and DILI without autoantibodies (DILIAb-, n = 75). The differential metabolites and fingerprint metabolites between AIH and DILIAb- were screened by orthogonal partial least squares-discriminant analysis and hierarchical clustering respectively. RESULTS: Of the 388 annotated differential metabolites between AIH and DILIAb-, 74 fingerprint metabolites were screened. The eigenmetabolite compressed from the fingerprint possessed high discrimination efficacy (AUC:0.891; 95 %CI, 0.838-0.944). In the fingerprint-based PCA model, AIH and DILIAb- were separated into three regions: the "pure region" of AIH (Region 1), the "pure region" of DILIAb- (Region 3), the mixture region of AIH and DILIAb- (Region 2). After incorporated into the PCA model, DILIAb+ samples were distributed into the three regions, indicating that DILIAb+ samples had different etiological tendencies. Moreover, the fingerprint-based radar model verified the results of PCA model characterizing DILIAb+. Notably, the antibody titers of DILIAb+ in the three regions did not differ significantly, while the response rates for glucocorticoids were obviously different. The metabolic difference among DILIAb+ in different regions mainly lies in energy metabolism. CONCLUSIONS: In terms of metabolic signature, DILIAb+ may not be a community of same pathogenesis, including AIH-inclined parts. Which deserves further study.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite Autoimune , Autoanticorpos , Humanos , Metabolômica
12.
Front Pharmacol ; 13: 896198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35668948

RESUMO

Background and aims: Chronic drug-induced liver injury (DILI) is a rare but under-researched adverse drug reaction-related disease, which is highly likely to progress into liver fibrosis and even cirrhosis. In this study, metabolomics was used to screen out characteristic metabolites related to the histological progression of fibrosis in chronic DILI and analyze the metabolic changes during the development of fibrosis to explain the underlying mechanism. Methods: Chronic DILI patients who underwent liver biopsy were divided into different fibrosis grades. Serum was analyzed by untargeted metabolomics to find serological characteristic metabolite fingerprints. The screened fingerprints were validated by the validation group patients, and the identification ability of fingerprints was compared using FibroScan. Results: A total of 31 metabolites associated with fibrosis and 11 metabolites associated with advanced fibrosis were identified. The validation group confirmed the accuracy of the two metabolite fingerprints [area under the curve (AUC) value 0.753 and 0.944]. In addition, the fingerprints showed the ability to distinguish the grades of fibrosis by comparing using FibroScan. The metabolite fingerprint pathway showed that bile acid synthesis is disturbed while lipid metabolism is extremely active, resulting in an overload of lipid metabolites in the occurrence and development of chronic DILI-associated fibrosis. Conclusions: Our metabolomic analysis reveals the unique metabolomic fingerprints associated with chronic DILI fibrosis, which have potential clinical diagnostic and prognostic significances. The metabolomic fingerprints suggest the disturbance of the lipid metabolites as the most important factor in the development of DILI fibrosis.

13.
Front Med (Lausanne) ; 9: 815467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35770013

RESUMO

Ascites is one of the most common complications of cirrhosis, and there is a dearth of knowledge about ascites-related pathologic metabolism. In this study, 122 alcoholic liver disease (ALD) patients, including 49 cases without ascites, 18 cases with mild-ascites, and 55 cases with large-ascites (1) were established according to the International Ascites Club (2), and untargeted metabolomics coupled with pattern recognition approaches were performed to profile and extract metabolite signatures. A total of 553 metabolites were uniquely discovered in patients with ascites, of which 136 metabolites had been annotated in the human metabolome database. Principal component analysis (PCA) analysis was used to further identify 21 ascites-related fingerprints. The eigenmetabolite calculated by reducing the dimensions of the 21 metabolites could be used to effectively identify those ALD patients with or without ascites. The eigenmetabolite showed a decreasing trend during ascites production and accumulation and was negatively related to the disease progress. These metabolic fingerprints mainly belong to the metabolites in lipid metabolism and the amino acid pathway. The results imply that lipid and amino acid metabolism disturbance may play a critical role in the development of ascites in ALD patients and could be a potent prognosis marker.

14.
Sci Total Environ ; 835: 155441, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35469881

RESUMO

With the rapid development of the mining industry, the pollution of heavy metal(loid)s in soils near copper (Cu) mining sites is a significant concern worldwide. However, the pollution status and probabilistic health risks of heavy metal(loid)s of soils associated with Cu mines, have rarely been studied on a global scale. In this study, eight heavy metal(loid) concentrations in soil samples taken near 102 Cu mining sites worldwide were obtained through a literature review. Based on this database, the heavy metal(loid) pollution and ecological risk in soils near Cu mines were evaluated. Most of the study sites exceeded the moderately to heavily polluted levels of Cu and Cd; compared to other regions, higher pollution levels were observed at sites in Oman, China, Australia, and the United Kingdom. Soil pollution by Cd, Pb, and Zn at agricultural sites was higher than that in non-agricultural sites. In addition, these heavy metal(loid)s produced a high ecological risk to soils around Cu mining sites in which the contribution of Cd, Cu, and As reached up to 46.5%, 21.7%, and 18.4%, respectively. The mean hazard indices of the eight heavy metal(loid)s were 0.209 and 0.979 for adults and children, respectively. The Monte Carlo simulation further predicted that 1.40% and 29.9% of non-carcinogenic risk values for adults and children, respectively, exceeded the safe level of 1.0. Moreover, 84.5% and 91.0% of the total cancer risk values for adults and children, respectively, exceeded the threshold of 1E-04. Arsenic was the main contributor to non-carcinogenic risk, while Cu had the highest exceedance of carcinogenic risk. Our findings indicate that the control of Cu, Cd, and As should be prioritized because of their high incidence and significant risks in soils near Cu mines. These results provide valuable inputs for policymakers in designing effective strategies for reducing the exposure of heavy metal(loid)s in this area worldwide.


Assuntos
Metais Pesados , Poluentes do Solo , Adulto , Cádmio/análise , Criança , China , Cobre/análise , Monitoramento Ambiental , Poluição Ambiental/análise , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
15.
Pharm Biol ; 60(1): 525-534, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35253576

RESUMO

CONTEXT: Keguan-1 (KG-1) plays a vital role in enhancing the curative effects, improving quality of life, and reducing the development of acute lung injury (ALI). OBJECTIVE: To unravel the protective effect and underlying mechanism of KG-1 against ALI. MATERIALS AND METHODS: C57BL/6J mice were intratracheally instilled with lipopolysaccharide to establish the ALI model. Then, mice in the KG-1 group received a dose of 5.04 g/kg for 12 h. The levels of proinflammatory cytokines, chemokines, and pathological characteristics were determined to explore the effects of KG-1. Next, untargeted metabolomics was used to identify the differential metabolites and involved pathways for KG-1 anti-ALI. Network pharmacology was carried out to predict the putative active components and drug targets of KG-1 anti-ALI. RESULTS: KG-1 significantly improved the levels of TNF-α (from 2295.92 ± 529.87 pg/mL to 1167.64 ± 318.91 pg/mL), IL-6 (from 4688.80 ± 481.68 pg/mL to 3604.43 ± 382.00 pg/mL), CXCL1 (from 4361.76 ± 505.73 pg/mL to 2981.04 ± 526.18 pg/mL), CXCL2 (from 5034.09 ± 809.28 pg/mL to 2980.30 ± 747.63 pg/mL), and impaired lung histological damage. Untargeted metabolomics revealed that KG-1 significantly regulated 12 different metabolites, which mainly related to lipid, amino acid, and vitamin metabolism. Network pharmacology showed that KG-1 exhibited anti-ALI effects through 17 potentially active components acting on seven putative drug targets to regulate four metabolites. DISCUSSION AND CONCLUSIONS: This work elucidated the therapeutic effect and underlying mechanism by which KG-1 protects against ALI from the view of the metabolome, thus providing a scientific basis for the usage of KG-1.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Modelos Animais de Doenças , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Farmacologia em Rede
16.
J Hazard Mater ; 426: 128084, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34952507

RESUMO

The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family of transcription factors and has broad biological functions. Early after the identification of the AHR, most studies focused on its roles in regulating the expression of drug-metabolizing enzymes and mediating the toxicity of dioxins and dioxin-like compounds (DLCs). Currently, more diverse functions of AHR have been identified, indicating that AHR is not just a dioxin receptor. Dioxins and DLCs occur ubiquitously and have diverse health/ecological risks. Additional research is required to identify both shared and compound-specific mechanisms, especially for emerging DLCs such as polyhalogenated carbazoles (PHCZs), polychlorinated diphenyl sulfides (PCDPSs), and others, of which only a few investigations have been performed at present. Many of the toxic effects of emerging DLCs were observed to be predominantly mediated by the AHR because of their structural similarity as dioxins, and the in vitro TCDD-relative potencies of certain emerging DLC congeners are comparable to or even greater than the WHO-TEFs of OctaCDD, OctaCDF, and most coplanar PCBs. Due to the close relationship between AHR biology and environmental science, this review begins by providing novel insights into AHR signaling (canonical and non-canonical), AHR's biochemical properties (AHR structure, AHR-ligand interaction, AHR-DNA binding), and the variations during AHR transactivation. Then, AHR ligand classification and the corresponding mechanisms are discussed, especially the shared and compound-specific, AHR-mediated effects and mechanisms of emerging DLCs. Accordingly, a series of in vivo and in vitro toxicity evaluation methods based on the AHR signaling pathway are reviewed. In light of current advances, future research on traditional and emerging DLCs will enhance our understanding of their mechanisms, toxicity, potency, and ecological impacts.


Assuntos
Dioxinas , Bifenilos Policlorados , Animais , Carbazóis , Dioxinas/toxicidade , Ratos , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/genética
17.
Plants (Basel) ; 10(11)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34834857

RESUMO

Kosteletzkya pentacarpos (L.) Ledebour is a perennial facultative halophyte species from the Malvacea family that grows in coastal areas with high amounts of salt. The tolerance of K. pentacarpos to the high concentration of salt (0.5-1.5% salinity range of coastal saline land) has been widely studied for decades. Nowadays, with the dramatic development of the economy and urbanization, in addition to the salt, the accumulation of mate(loid)s in coastal soil is increasing, which is threatening the survival of halophyte species as well as the balance of wetland ecosystems. Recently, the capacity of K. pentacarpos to cope with either single heavy metal stress or a combination of multiple meta(loid) toxicities was studied. Hence, this review focused on summarizing the physiological and biochemical behaviors of K. pentacarpos that has been simultaneously exposed to the combination of several meta(loid) toxicities. How the salt accumulated by K. pentacarpos impacts the response to meta(loid) stress was discussed. We conclude that as a potential candidate for phytoremediation, K. pentacarpos was able to cope with various environmental constrains such as multiple meta(loid) stresses due to its relative tolerance to meta(loid) toxicity.

18.
Front Pharmacol ; 12: 693928, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630079

RESUMO

Early identification of individuals susceptible to idiosyncratic drug-induced liver injury (IDILI) is a challenging unmet demand. Diclofenac, one of the most widely available over-the-counter drugs for pain management worldwide, may induce liver dysfunction, acute liver failure, and death. Herein, we report that diclofenac-related hepatobiliary adverse reactions occurred more frequently in cases with immune activation. Furthermore, experiments with rats demonstrated divergent hepatotoxicity responses in individuals exposed to diclofenac, and modest inflammation potentiated diclofenac-induced liver injury. Susceptible rats had unique plasma metabolomic characteristics, and as such, the metabolomic approach could be used to distinguish susceptible individuals. The 23 identified susceptibility-related metabolites were enriched by several metabolic pathways related to acute-phase reactions of immunocytes and inflammatory responses, including sphingolipid, tyrosine, phenylalanine, tryptophan, and lipid metabolism pathways. This finding implies a mechanistic role of metabolic and immune disturbances affects susceptibility to diclofenac-IDILI. Further nine metabolite biomarkers with potent diagnostic capabilities were identified using receiver operating characteristic curves. These findings elucidated the potential utility of metabolomic biomarkers to identify individuals susceptible to drug hepatotoxicity and the underlying mechanism of metabolic and immune disturbances occurring in IDILI.

19.
J Food Biochem ; 45(5): e13737, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33876445

RESUMO

Areca nut and Fuzhuan brick tea, a type of natural plant products, have obvious effects of fat reduction and weight loss; however, there is no report on their synergistic effect. This study investigated the effects of Fuzhuan brick tea supplemented with different concentrations of areca nut (5% (LAF), 10% (MAF), and 20% (HAF)) on serum and gut microbiota in Kunming (KM) mice. The results showed that Fuzhuan brick tea supplemented with areca nuts (AFTs) could reduce weight, prevent the accumulation of fat, inhibit the increase in the levels of serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, blood glucose, free fatty acid, insulin, and total bile acid, alleviate the decrease in high-density lipoprotein cholesterol level, and regulate the composition of gut microbiota by high-fat diet intervention. The HAF group with 20% areca nut content showed the best effect. These results could provide a novel approach to prevent obesity and hyperlipidemia. PRACTICAL APPLICATIONS: Consumption of areca nut and tea is widespread in Asia and other regions. As a controversial raw material, the damage due to areca nut to oral mucosa health has often aroused public concern and heated discussion; however, its medicinal value has been confirmed in terms of its pharmacological effects in various aspects. Fuzhuan brick tea, a type of traditional postfermented dark tea, has been confirmed to exert effects of antiobesity. Therefore, the areca nut and Fuzhuan brick tea, as a type of natural plant products, have obvious effects of fat reduction and weight loss; however, their synergistic effect has not been reported. To our knowledge, this study is the first to explore the effects of the Fuzhuan brick tea supplemented with areca nuts (AFTs) on serum and gut microbiota in mice. On the premise of exerting their beneficial effects (especially in terms of easing food stagnation and eliminating indigestion) and reducing their toxic and side effects, the effects of AFTs on health were further clarified, which could provide a novel direction for the development and utilization of areca nut. Moreover, our research would increase public understanding of areca nut and provide guidance to the Fuzhuan brick tea processing industry.


Assuntos
Microbioma Gastrointestinal , Animais , Areca , Dieta Hiperlipídica/efeitos adversos , Camundongos , Nozes , Chá
20.
J Acoust Soc Am ; 148(3): 1756, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33003885

RESUMO

Perforated plates are widely used in many practical burners to attenuate noise emissions. In this study, the acoustic absorption capability of dual perforated plates (DPPs) with different porosities and aperture diameters was evaluated and tested in an impedance tube, and the damping performance of the DPPs located in a liquid fuel combustor inlet section was experimentally studied. The DPPs have an adjustable first cavity and can mitigate the thermoacoustic oscillations within a wide sound absorption bandwidth. The DPPs can absorb 95% of the specified incident sound energy. The combustion results indicated that the installation of DPPs at the inlet section has two effects: sound attenuation and the frequency shift of the combustor. The maximum reduction in dynamic pressure and CH* chemiluminescence intensity inside the chamber were 14 and 19 dB, respectively. When the primary air flow rate deviates from the optimal value, the DPPs can reduce the pressure amplitude in the combustion chamber by almost 80%. In general, this study may promote the application of DPPs under bias flow for the stabilization of spray combustion.

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