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Patients with chronic pain often experience memory impairment, but the underlying mechanisms remain elusive. The myelin sheath is crucial for rapid and accurate action potential conduction, playing a pivotal role in the development of cognitive abilities in the central nervous system. The study reveals that myelin degradation occurs in the hippocampus of chronic constriction injury (CCI) mice, which display both chronic pain and memory impairment. Using fiber photometry, we observed diminished task-related neuronal activity in the hippocampus of CCI mice. Interestingly, the repeated administration with clemastine, which promotes myelination, counteracts the CCI-induced myelin loss and reduced neuronal activity. Notably, clemastine specifically ameliorates the impaired memory without affecting chronic pain in CCI mice. Overall, our findings highlight the significant role of myelin abnormalities in CCI-induced memory impairment, suggesting a potential therapeutic approach for treating memory impairments associated with neuropathic pain.
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Dolor Crónico , Clemastina , Humanos , Animales , Ratones , Clemastina/metabolismo , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/metabolismo , Vaina de Mielina/metabolismo , Sistema Nervioso Central , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Hipocampo/metabolismoRESUMEN
As a model liverwort, Marchantia polymorpha contains various flavone glucuronides with cardiovascular-promoting effects and anti-inflammatory properties. However, the related glucuronosyltransferases have not yet been reported. In this study, two bifunctional UDP-glucuronic acid/UDP-glucose:flavonoid glucuronosyltransferases/glucosyltransferases, MpUGT742A1 and MpUGT736B1, were identified from M. polymorpha. Extensive enzymatic assays found that MpUGT742A1 and MpUGT736B1 exhibited efficient glucuronidation activity for flavones, flavonols, and flavanones and showed promiscuous regioselectivity at positions 3, 6, 7, 3', and 4'. These enzymes catalyzed the production of a variety of flavonoid glucuronides with medicinal value, including apigenin-7-O-glucuronide and scutellarein-7-O-glucuronide. With the use of MpUGT736B1, apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide were prepared by scaled-up enzymatic catalysis and structurally identified by NMR spectroscopy. MpUGT742A1 also displayed glucosyltransferase activity on the 7-OH position of the flavanones using UDP-glucose as the sugar donor. Furthermore, we constructed four recombinant strains by combining the pathway for increasing the UDP-glucuronic acid supply with the two novel UGTs MpUGT742A1 and MpUGT736B1. When apigenin was used as a substrate, the extracellular apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide production obtained from the Escherichia coli strain BB2 reached 598 and 81 mg/L, respectively. Our study provides new candidate genes and strategies for the biosynthesis of flavonoid glucuronides.
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Flavanonas , Marchantia , Flavonoides/química , Apigenina , Glucurónidos/metabolismo , Marchantia/metabolismo , Glucuronosiltransferasa/química , Glucuronosiltransferasa/metabolismo , Escherichia coli/metabolismo , Glucosa , Ácido Glucurónico , Uridina DifosfatoRESUMEN
Family 1 UDP-glycosyltransferases (UGTs) are known to glycosylate multiple secondary plant metabolites and have been extensively studied. The increased availability of plant genome resources allows the identification of wide gene families, both functional and organizational. In this investigation, two MpUGT isoforms were cloned and functionally characterized from liverworts marchantia polymorpha and had high glycosylation activity against several flavonoids. MpUGT735A2 protein, in particular, tolerates a wide spectrum of substrates (flavonols, flavanones, flavones, stilbenes, bibenzyls, dihydrochalcone, phenylpropanoids, xanthones, and isoflavones). Overexpression of MpUGT735A2 and MpUGT743A1 in Arabidopsis thaliana enhances the accumulation of 3-O-glycosylated flavonol (kaempferol 3-O-glucoside-7-O-rhamnose), consistent with its in vitro enzymatic activity. Docking and mutagenesis techniques were applied to identify the structural and functional properties of MpUGT735A2 with promiscuous substrates. Mutation of Pro87 to Ser, or Gln88 to Val, substantially altered the regioselectivity for luteolin glycosylation, predominantly from the 3'-O- to the 7-O-position. The results were elucidated by focusing on the novel biocatalysts designed for producing therapeutic flavonoids. This investigation provides an approach to modulate MpUGT735A2 as a candidate gene for diverse glycosylation catalysis and a tool to design GTs with new substrate specificities for biomedical applications.
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Unlike bibenzyls derived from the vascular plants, lunularic acid (LA), a key precursor for macrocyclic bisbibenzyl synthesis in nonvascular liverworts, exhibits the absence of one hydroxy group within the A ring. It was hypothesized that both polyketide reductase (PKR) and stilbenecarboxylate synthase 1 (STCS1) were involved in the LA biosynthesis, but the underlined mechanisms have not been clarified. This study used bioinformatics analysis with molecular, biochemical and physiological approaches to characterize STCS1s and PKRs involved in the biosynthesis of LA. The results indicated that MpSTCS1s from Marchantia polymorpha catalyzed both C2âC7 aldol-type and C6âC1 Claisen-type cyclization using dihydro-p-coumaroyl-coenzyme A (CoA) and malonyl-CoA as substrates to yield a C6-C2-C6 skeleton of dihydro-resveratrol following decarboxylation and the C6-C3-C6 type of phloretin in vitro. The protein-protein interaction of PKRs with STCS1 (PPI-PS) was revealed and proved essential for LA accumulation when transiently co-expressed in Nicotiana benthamiana. Moreover, replacement of the active domain of STCS1 with an 18-amino-acid fragment from the chalcone synthase led to the PPI-PS greatly decreasing and diminishing the formation of LA. The replacement also increased the chalcone formation in STCS1s. Our results highlight a previously unrecognized PPI in planta that is indispensable for the formation of LA.
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Marchantia , Salicilatos , Coenzima A/químicaRESUMEN
OBJECTIVE: Despite widespread recognition, the mechanisms underlying the relationship between systemic lupus erythematosus (SLE) and atherosclerosis (AS) are still unclear. Our study aimed to explore the shared genetic signature and molecular mechanisms of SLE and AS using a bioinformatics approach. METHODS: Gene expression profiles of GSE50772 (contains peripheral blood mononuclear cells from 61 SLE patients and 20 normal samples) and GSE100927 (contains 69 AS plaque tissue samples and 35 control samples) were downloaded from the Gene Expression Database (GEO) before the differentially expressed genes were obtained using the "limma" package in R. The differential genes were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the DAVID online platform to annotate their functions. The intersection targets of PPI and WGCNA were used as key shared genes for SLE and AS with their diagnostic value as shared genes being verified through ROC curves. Finally, Cytoscape 3.7.2 software was used to construct a miRNA-mRNA network map associated with the shared genes. RESULTS: A total of 246 DEGs were identified, including 189 upregulated genes and 57 downregulated genes, which were mainly enriched in signaling pathways such as TNF signaling pathway, IL-17 signaling pathway, and NF-kB signaling pathway. The molecular basis for the relationship between SLE and AS may be the aforementioned signaling pathways. Following ROC curve validation, the intersection of PPI and WGCNA, as well as AQP9, CCR1, CD83, CXCL1, and FCGR2A, resulted in the identification of 15 shared genes. CONCLUSION: The study provided a new perspective on the common molecular mechanisms between SLE and AS, and the key genes and pathways that were identified as being part of these pathways may offer fresh perspectives and suggestions for further experimental research.
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Aterosclerosis , Lupus Eritematoso Sistémico , MicroARNs , Humanos , Leucocitos Mononucleares , Lupus Eritematoso Sistémico/genética , Transcriptoma , Aterosclerosis/genética , Biología Computacional/métodos , Perfilación de la Expresión GénicaRESUMEN
INTRODUCTION: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment. METHODS: Both female and male mice received a single intraperitoneal injection of 100 µg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining. RESULTS: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis. CONCLUSIONS: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.
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Lipopolisacáridos , Fosfopéptidos , Animales , Masculino , Femenino , Ratones , Lipopolisacáridos/toxicidad , Fosfopéptidos/efectos adversos , Fosfopéptidos/metabolismo , Proteómica , Inflamación/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismoRESUMEN
Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood-brain barrier with difficulties reaching the central nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood-brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study.
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Melaninas , Nanopartículas , Ratones , Animales , Depresión/tratamiento farmacológico , Nanopartículas/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológicoRESUMEN
BACKGROUND: This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score and renal venous Doppler waveform (RVDW) pattern in predicting acute kidney injury (AKI) in critically ill patients and establish prediction models. METHODS: This prospective observational study included 234 critically ill patients. Renal ultrasound was measured within 24 h after intensive care unit admission. The main outcome was the highest AKI stage within 5 days after admission according to the Kidney Disease Improving Global Outcomes criteria. RESULTS: Patients in the AKI stage 3 group had significantly higher RRI, RVDW pattern and lower PDU score (p < 0.05). Only lactate, urine volume, serum creatinine (SCr) on admission, PDU score and RVDW pattern were statistically significant predictors (p < 0.05). Model 1 based on these five variables (area under the curve [AUC] = 0.938, 95% confidence interval [CI] 0.899-0.965, p < 0.05) showed the best performance in predicting AKI stage 3, and difference in AUC between it and the clinical model including lactate, urine volume and SCr (AUC = 0.901, 95% CI 0.855-0.936, p < 0.05) was statistically significant (z statistic = 2.224, p = 0.0261). The optimal cut-off point for a nomogram based on Model 1 was ≤127.67 (sensitivity: 95.8%, specificity: 82.3%, Youden's index: 0.781). CONCLUSIONS: The nomogram model including SCr, urine volume, lactate, PDU score and RVDW pattern upon admission exhibited a significantly stronger capability for AKI stage 3 than each single indicator and clinical model including SCr, urine volume and lactate.
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Lesión Renal Aguda , Enfermedad Crítica , Humanos , Ultrasonografía Doppler , Ultrasonografía , Lesión Renal Aguda/diagnóstico por imagen , Ácido LácticoRESUMEN
Exoelectrogenic bacteria (EEB) are capable of anaerobic respiration with diverse extracellular electron acceptors including insoluble minerals, electrodes and flavins, but the detailed electron transfer pathways and reaction mechanisms remain elusive. Here, we discover that CymA, which is usually considered to solely serve as an inner-membrane electron transfer hub in Shewanella oneidensis MR-1 (a model EEB), might also function as a reductase for direct reducing diverse nitroaromatic compounds (e.g. 2,4-dichloronitrobenzene) and azo dyes. Such a process can be accelerated by dosing anthraquinone-2,6-disulfonate. The CymA-based reduction pathways in S. oneidensis MR-1 for different contaminants could be functionally reconstructed and strengthened in Escherichia coli. The direct reduction of lowly polar contaminants by quinol oxidases like CymA homologues might be universal in diverse microbes. This work offers new insights into the pollutant reduction mechanisms of EEB and unveils a new function of CymA to act as a terminal reductase.
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Contaminantes Ambientales , Shewanella , Transporte de Electrón , Electrones , Contaminantes Ambientales/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Oxidación-Reducción , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Shewanella/metabolismoRESUMEN
BACKGROUND: Flavonoid C-glycosides have many beneficial effects and are widely used in food and medicine. However, plants contain a limited number of flavonoid C-glycosides, and it is challenging to create these substances chemically. RESULTS: To screen more robust C-glycosyltransferases (CGTs) for the biosynthesis of flavonoid C-glycosides, one CGT enzyme from Stenoloma chusanum (ScCGT1) was characterized. Biochemical analyses revealed that ScCGT1 showed the C-glycosylation activity for phloretin, 2-hydroxynaringenin, and 2-hydroxyeriodictyol. Structure modeling and mutagenesis experiments indicated that the glycosylation of ScCGT1 may be initiated by the synergistic action of conserved residue His26 and Asp14. The P164T mutation increased C-glycosylation activity by forming a hydrogen bond with the sugar donor. Furthermore, when using phloretin as a substrate, the extracellular nothofagin production obtained from the Escherichia coli strain ScCGT1-P164T reached 38 mg/L, which was 2.3-fold higher than that of the wild-type strain. Finally, it is proved that the coupling catalysis of CjFNS I/F2H and ScCGT1-P164T could convert naringenin into vitexin and isovitexin. CONCLUSION: This is the first time that C-glycosyltransferase has been characterized from fern species and provides a candidate gene and strategy for the efficient production of bioactive C-glycosides using enzyme catalysis and metabolic engineering.
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Helechos , Glicosiltransferasas , Escherichia coli/metabolismo , Helechos/metabolismo , Flavonoides/metabolismo , Glicósidos , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Floretina , AzúcaresRESUMEN
The biotransformation of heavy metals in the environment is usually affected by co-existing pollutants like selenium (Se), which may lower the ecotoxicity of heavy metals, but the underlying mechanisms remain unclear. Here, we shed light on the pathways of copper (Cu2+) and selenite (SeO32-) synergistic biodetoxification by Shewanella oneidensis MR-1 and illustrate how such processes are affected by anthraquinone-2,6-disulfonate (AQDS), an analogue of humic substances. We observed the formation of copper selenide nanoparticles (Cu2-xSe) from synergistic detoxification of Cu2+ and SeO32- in the periplasm. Interestingly, adding AQDS triggered a fundamental transition from periplasmic to extracellular reaction, enabling 14.7-fold faster Cu2+ biodetoxification (via mediated electron transfer) and 11.4-fold faster SeO32- detoxification (via direct electron transfer). This is mainly attributed to the slightly raised redox potential of the heme center of AQDS-coordinated outer-membrane proteins that accelerates electron efflux from the cells. Our work offers a fundamental understanding of the synergistic detoxification of heavy metals and Se in a complicated environmental matrix and unveils an unexpected role of AQDS beyond electron mediation, which may guide the development of more efficient environmental remediation and resource recovery biotechnologies.
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Contaminantes Ambientales , Selenio , Antraquinonas , Cobre , Hemo , Sustancias Húmicas , Proteínas de la Membrana , Oxidación-Reducción , Ácido SeleniosoRESUMEN
Due to the potential hazard of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (HFPO-DA, GenX) has become a typical alternative since 2009. However, GenX has recently been reported to have equal or even greater toxicity and bioaccumulation than PFOA. Considering the suitability of alternatives, it is quite essential to study and compare the degradation degree between PFOA and GenX in water. Therefore, in the present study, a comprehensive degradation comparison between them via electrooxidation with a titanium suboxide membrane anode was conducted. The degradation rate decreased throughout for PFOA, while it first increased and then decreased for GenX when the permeate flux increased from 17.3 L to 100.3 L m-2·h-1. The different responses of PFOA and GenX to flux might be attributed to their different solubilities. In addition, the higher kobs of PFOA demonstrated that it had a better degradability than GenX by 2.4-fold in a mixed solution. The fluorinated byproduct perfluoropropanoic acid (PFPrA) was detected as a GenX intermediate, suggesting that ether bridge splitting was needed for GenX electrooxidation. This study provides a reference for assessing the degradability of GenX and PFOA and indicates that it is worth reconsidering whether GenX is a suitable alternative for PFOA from the point of view of environmental protection.
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Fluorocarburos , Contaminantes Químicos del Agua , Bioacumulación , Caprilatos , Fluorocarburos/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbeanins P-Q (1-2), and two new biosynthetic precursors, hyperbeanins R-S (3-4), were isolated from Hypericum beanii, together with three known analogs (5-7). Compound 1 was one of type A PPAPs featured with unusual bicyclo[5.3.1]hendecane core. The structures of isolates were established by NMR spectroscopic methods, experimental electronic circular dichroism (ECD) spectra and comparisons with known compounds. Compounds 5 and 6 showed obvious hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage.
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Hypericum , Humanos , Hypericum/química , Floroglucinol , Estructura Molecular , Células Hep G2 , Espectroscopía de Resonancia MagnéticaRESUMEN
The key enzymes involved in the flavonoid biosynthesis pathway have been extensively studied in seed plants, but relatively less in ferns. In this study, two 4-Coumarate: coenzyme A ligases (Sc4CL1 and Sc4CL2) and one novel chalcone synthase (ScCHS1) were functionally characterized by mining the Stenoloma chusanum transcriptome database. Recombinant Sc4CLs were able to esterify various hydroxycinnamic acids to corresponding acyl-coenzyme A (CoA). ScCHS1 could catalyze p-coumaroyl-CoA, cinnamoyl-CoA, caffeoyl-CoA, and feruloyl-CoA to form naringenin, pinocembrin, eriodictyol, and homoeriodictyol, respectively. Moreover, enzymatic kinetics studies revealed that the optimal substrates of ScCHS1 were feruloyl-CoA and caffeoyl-CoA, rather than p-coumaroyl-CoA, which was substantially different from the common CHSs. Crystallographic and site-directed mutagenesis experiments indicated that the amino acid residues, Leu87, Leu97, Met165, and Ile200, located in the substrate-binding pocket near the B-ring of products, could exert a significant impact on the unique catalytic activity of ScCHS1. Furthermore, overexpression of ScCHS1 in tt4 mutants could partially rescue the mutant phenotypes. Finally, ScCHS1 and Sc4CL1 were used to synthesize flavanones and flavones with multi-substituted hydroxyl and methoxyl B-ring in Escherichia coli, which can effectively eliminate the need for the cytochrome P450 hydroxylation/O-methyltransferase from simple phenylpropanoid acids. In summary, the identification of these important Stenoloma enzymes provides a springboard for the future production of various flavonoids in E. coli.
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Helechos , Flavanonas , Flavonas , Secuencia de Aminoácidos , Helechos/genética , Ácidos Cumáricos , Escherichia coli/genética , Escherichia coli/metabolismo , Flavanonas/metabolismo , Flavonoides/metabolismo , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Metiltransferasas/metabolismo , AminoácidosRESUMEN
During the course of evolution of land plants, different classes of flavonoids, including flavonols and anthocyanins, sequentially emerged, facilitating adaptation to the harsh terrestrial environment. Flavanone 3ß-hydroxylase (F3H), an enzyme functioning in flavonol and anthocyanin biosynthesis and a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) family, catalyzes the hydroxylation of (2S)-flavanones to dihydroflavonols, but its origin and evolution remain elusive. Here, we demonstrate that functional flavone synthase Is (FNS Is) are widely distributed in the primitive land plants liverworts and evolutionarily connected to seed plant F3Hs. We identified and characterized a set of 2-ODD enzymes from several liverwort species and plants in various evolutionary clades of the plant kingdom. The bifunctional enzyme FNS I/F2H emerged in liverworts, and FNS I/F3H evolved in Physcomitrium (Physcomitrella) patens and Selaginella moellendorffii, suggesting that they represent the functional transition forms between canonical FNS Is and F3Hs. The functional transition from FNS Is to F3Hs provides a molecular basis for the chemical evolution of flavones to flavonols and anthocyanins, which contributes to the acquisition of a broader spectrum of flavonoids in seed plants and facilitates their adaptation to the terrestrial ecosystem.
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Antocianinas/biosíntesis , Antocianinas/genética , Embryophyta/genética , Embryophyta/metabolismo , Flavonas/genética , Flavonas/metabolismo , Flavonoles/biosíntesis , Flavonoles/genética , Evolución Química , Evolución Molecular , Regulación de la Expresión Génica de las Plantas , Genes de PlantasRESUMEN
OBJECTIVE: A number of studies have suggested a pathophysiological link between allergic diseases and epilepsy. Understanding the association between allergic diseases and epilepsy can help establish healthcare policies, implement prevention strategies, and provide a new direction for treatment. The study aimed to examine the association between allergic diseases and epilepsy. METHODS: PubMed, EMBASE, and Web of Science were searched for relevant primary articles. Two individuals independently conducted abstract screening, full-text review, data extraction, and quality assessment. Random-effects models were used to pool the risk estimates. RESULTS: From the 3124 citations identified, 32 were reviewed in full text. Finally, 11 studies with a total of 3,312,033 subjects were eligible for the analyses. Few studies reported the type of epilepsy, and there were inconsistent attempts to control for confounding. The pooled result showed that there was an 81% increase in the prevalence of epilepsy among individuals with asthma compared with those without asthma (odds ratio: 1.81, 95% confidence interval [CI]:1.47-2.21). The incidence of epilepsy in patients with eczema was 2.57 (95%CI: 1.54-4.27). Sensitivity analyses confirmed that no single study qualitatively influenced the pooled OR. All funnel plots were asymmetric upon visual inspection, suggesting publication bias. CONCLUSION: Our findings suggest that patients with allergic diseases might have a high risk of epilepsy. Additional high-quality primary studies are required to confirm the association, obtain information regarding the mechanism of association, and determine prevention opportunities.
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Epilepsia , Epilepsia/complicaciones , Epilepsia/epidemiología , Humanos , Incidencia , Oportunidad Relativa , PrevalenciaRESUMEN
BACKGROUND: Phenylketonuria (PKU) is a genetic metabolic disorder in which patients have no ability to convert phenylalanine to tyrosine. Several autoimmune diseases have been reported to combine with PKU, co-existent of PKU and Juvenile Idiopathic Arthritis (JIA) has not been presented. CASE PRESENTATION: The girl was diagnosed with PKU at the age of 1 month confirmed by molecular data. At the age of 3.5 years, she presented with pain and swelling of her right ankle, right knee, and right hip joint. After a serial of examinations, she was diagnosed with JIA and treated with a nonsteroidal anti-inflammatory drug. CONCLUSIONS: We report a rare case of a 4-year-old girl with PKU and JIA, which supports a possible interaction between PKU and JIA. Long-term metabolic disturbance may increase the susceptibility to JIA. Further chronic inflammation could alter the metabolism of tryptophan and tyrosine to increase blood Phe concentration. In addition, corticosteroid and methotrexate therapy for JIA may increase blood Phe concentration.
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Artritis Juvenil , Fenilcetonurias , Corticoesteroides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico , Artritis Juvenil/tratamiento farmacológico , Preescolar , Femenino , Humanos , Fenilalanina , Fenilcetonurias/complicaciones , Fenilcetonurias/diagnósticoRESUMEN
Mercury (Hg), as a highly harmful environmental pollutant, poses severe ecological and health risks even at low concentrations. Accurate and sensitive methods for detecting Hg2+ ions in aquatic environments are highly needed. In this work, we developed a highly sensitive fluorescence sensor for Hg2+ detection with an integrated use of biosynthetic CdSe/CdS quantum dots (QDs) and liposome carrier signal amplification. To construct such a sensor, three single-stranded DNA probes were rationally designed based on the thymine-Hg2+-thymine (T-Hg2+-T) coordination chemical principles and by taking advantage of the biocompatibility and facile-modification properties of the biosynthetic QDs. Hg2+ could be determined in a range from 0.25 to 100 nM with a detection limit of 0.01 nM, which met the requirements of environmental sample detection. The sensor also exhibited a high selectivity for Hg2+ detection in the presence of other high-level metal ions. A satisfactory capacity of the sensor for detecting environmental samples including tap water, river water, and landfill leachate was also demonstrated. This work opens up a new application scenario for biosynthetic QDs and holds a great potential for environmental monitoring applications.
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Liposomas/química , Mercurio/análisis , Puntos Cuánticos/química , Espectrometría de Fluorescencia/métodos , Compuestos de Cadmio/química , ADN de Cadena Simple/química , Monitoreo del Ambiente , Agua Dulce/análisis , Concentración de Iones de Hidrógeno , Límite de Detección , Compuestos de Selenio/química , Sulfuros/química , Timina/química , Contaminantes Químicos del Agua/análisisRESUMEN
The distribution of type I and II chalcone isomerases (CHIs) in plants is highly family specific. We have previously reported that ancient land plants, such as the liverworts and Selaginella moellendorffii, harbor type II CHIs. To better understand the function and evolution of CHI-fold proteins, transcriptomic data obtained from 52 pteridophyte species were subjected to sequence alignment and phylogenetic analysis. The residues determining type I/II CHI identity in the pteridophyte CHIs were identical to those of type I CHIs. The enzymatic characterization of a sample of 24 CHIs, representing all the key pteridophyte lineages, demonstrated that 19 of them were type I enzymes and that five exhibited some type II activity due to an amino acid mutation. Two pteridophyte chalcone synthases (CHSs) were also characterized, and a type IV CHI (CHIL) was demonstrated to interact physically with CHSs and CHI, and to increase CHS activity by decreasing derailment products, thus enhancing flavonoid production. These findings suggest that the emergence of type I CHIs may have coincided with the divergence of the pteridophytes. This study deepens our understanding of the molecular mechanism of CHIL as an enhancer in the flavonoid biosynthesis pathway.
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Evolución Molecular , Helechos/genética , Liasas Intramoleculares/genética , Proteínas de Plantas/genética , Secuencia de Aminoácidos , Helechos/enzimología , Liasas Intramoleculares/química , Liasas Intramoleculares/metabolismo , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Alineación de SecuenciaRESUMEN
Biotransformation of selenite to valuable elemental selenium nanoparticles (Se0) is a promising avenue to remediate seleniferous environments and simultaneously recover selenium (Se). However, the underlying oxyanion competition and selenite transformation mechanism in prokaryotes are poorly understood. In this work, the impacts of phosphate on selenite uptake and transformation were elucidated with Escherichia coli and its mutant deficient in phosphate transport as model microbial strains. Selenite uptake was inhibited by phosphate in E. coli. Moreover, the transformation of internalized Se was shifted from Se0 to toxic organo-Se with elevated phosphate levels, as evidenced by the linear combination fit analysis of the Se K-edge X-ray absorption near-edge structure. Such a phosphate-regulated selenite biotransformation process was mainly assigned to the competitive uptake of phosphate and selenite, which was primarily mediated by a low affinity phosphate transporter (PitA). Under phosphate-deficient conditions, the cells not only produced abundant Se0 nanoparticles but also maintained good cell viability. These findings provide new insights into the phosphate-regulated selenite biotransformation by prokaryotes and contribute to the development of new processes for bioremediating Se-contaminated environments, as well as bioassembly of Se0.