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AIM: To examine association between subgingival microbial signatures and levels of cognitive impairment in older adults. MATERIALS AND METHODS: We analysed subgingival plaque samples and 16S ribosomal RNA sequences for microbiota among 165 participants (normal controls [NCs]: 40, subjective cognitive decline [SCD]: 40, mild cognitive impairment [MCI]: 49 and dementia: 36). RESULTS: The bacterial richness was lower among individuals with worse cognitive function, and subgingival microbial communities differed significantly among the four groups. Declining cognitive function was associated with decreasing relative abundance of genera Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia and Granulicatella, and increasing abundance of genus Porphyromonas. Moreover, there were differentially abundant genera among the groups. Random forest model based on subgingival microbiota could distinguish between cognitive impairment and NC (AUC = 0.933, 95% confidence interval 0.873-0.992). Significant correlations were observed between oral microbiota and sex, Montreal Cognitive Assessment (MoCA) score and Mini-Mental State Examination score. Partial correlation analysis showed that Leptotrichia and Burkholderia were closely negatively associated with the MoCA score after adjusting for multiple covariates. Gene function was not significantly different between SCD and NC groups, whereas three homozygous genes were altered in MCI patients and two in dementia patients. CONCLUSIONS: This is the first study to demonstrate an association between the composition, function and metabolic pathways of subgingival microbiota and different levels of cognitive function among older individuals. Future cohort studies should assess its diagnostic usefulness for cognitive impairment.
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Disfunção Cognitiva , Microbiota , Humanos , Idoso , Feminino , Masculino , Disfunção Cognitiva/microbiologia , Demência/microbiologia , Cognição/fisiologia , RNA Ribossômico 16S/análise , Gengiva/microbiologia , Placa Dentária/microbiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
Diet can regulate systemic inflammation, which may play an important role in the development and progression of cognitive impairment and dementia. To explore the relationship between the dietary inflammatory potential and cognitive ability. A total of 2307 adults aged 60 years or older were recruited from the Fujian Provincial Hospital (Fujian, China). Dietary inflammatory properties were analyzed using the energy-adjusted dietary inflammatory index (E-DII). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. Logistic regression and restricted cubic spline (RCS) were fit to assess the associations between variables. The MCI subjects with the highest E-DII scores had a higher risk of AD compared to subjects with the lowest E-DII scores (OR = 1.98, 95%CI = 1.49-2.64, P for trend < 0.001). Subjects with the highest E-DII levels were at increased risk of cognitive impairment compared to those with the lowest E-DII levels (OR = 1.56, 95%CI = 1.25-1.93, P for trend < 0.001). The link between E-DII and cognitive impairment was significant in a nonlinear dose response analysis (P for nonlinear = 0.001). Higher E-DII scores were associated with an increased risk of developing AD or cognitive impairment. These findings may contribute to the effective prevention of cognitive impairment by constructing a multidisciplinary synergistic prevention strategy and controlling dietary inflammation levels.
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We explored the effects of an oral health intervention on the oral microbiome and cognitive function of patients with mild Alzheimer's disease (AD) and determined the influence on disease progression. Sixty-six patients with mild AD were randomly assigned to intervention or control groups and received a 24-week oral health intervention and routine care, respectively. Data were collected at baseline and week 24. 16 S rRNA sequencing was used to analyze oral microbiota. After 24 weeks of oral health intervention, Kayser-Jones Brief Oral Health Status Examination (BOHSE), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Nursing Home Adjustment Scale (NHAS), and Alzheimer's Disease Cooperative Study-ADL (ADCS-ADL) scores were different between groups (p < 0.05). Subgingival plaque in patients with AD showed significant differences in the diversity and abundance of oral microbiomes, with a higher abundance of normal oral flora in the intervention group. We found oral health intervention strategies are effective in modifying subgingival microbiota differences and slowing cognitive decline in mild AD patients.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/psicologia , Saúde Bucal , Cognição , Casas de SaúdeRESUMO
Microbial siderophores are multidentate Fe(III) chelators used by microbes during siderophore-mediated assimilation. They possess high affinity and selectivity for Fe(III). Among them, marine siderophore-mediated microbial iron uptake allows marine microbes to proliferate and survive in the iron-deficient marine environments. Due to their unique iron(III)-chelating properties, delivery system, structural diversity, and therapeutic potential, marine microbial siderophores have great potential for further development of various drug conjugates for antibiotic-resistant bacteria therapy or as a target for inhibiting siderophore virulence factors to develop novel broad-spectrum antibiotics. This review covers siderophores derived from marine microbes.
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Organismos Aquáticos/química , Bactérias/química , Quelantes/química , Sideróforos/química , Antibacterianos/química , Antibacterianos/farmacologia , Organismos Aquáticos/metabolismo , Bactérias/metabolismo , Quelantes/isolamento & purificação , Desenvolvimento de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Ferro/química , Ferro/metabolismo , Microbiota , Sideróforos/antagonistas & inibidores , Sideróforos/isolamento & purificação , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/química , Fatores de Virulência/isolamento & purificaçãoRESUMO
Quorum sensing inhibitors (QSIs) present a promising alternative or potent adjuvants of conventional antibiotics for the treatment of antibiotic-resistant bacterial strains, since they could disrupt bacterial pathogenicity without imposing selective pressure involved in antibacterial treatments. This review covers a series of molecules showing quorum sensing (QS) inhibitory activity that are isolated from marine microorganisms, including bacteria, actinomycetes and fungi, and chemically synthesized based on QSIs derived from marine microorganisms. This is the first comprehensive overview of QSIs derived from marine microorganisms and their synthetic analogues with QS inhibitory activity.
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Antibacterianos/farmacologia , Organismos Aquáticos , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana , Fungos/metabolismo , Percepção de Quorum/efeitos dos fármacos , Bactérias/metabolismoRESUMO
The natural products discovery program in our group utilizes deep-sea sediment-derived microorganisms and employs a bio-active guided isolation procedure and one strain many compounds (OSMAC) approach to screen bio-active natural products for practical applications in the medicinal and agricultural industry. OSMAC strategy is employed to stimulate secondary metabolite production through changing culture conditions. In this paper, we applied cultivation-dependent procedure, changing media type, leading to the discovery of a bio-active compound named inthomycin B (1) from a marine-derived Streptomyces sp. YB104. The compound was characterized based on extensive spectroscopic analyses and comparison to that in the reported literature. The quantification of inthomycin B demonstrated that Streptomyces sp. YB104 produced moderate yield of inthomycin B with a yield around 25 mg/l after 14 days. Thus, Streptomyces sp. YB104 was considered to be a useful potential as a first industrial-producing strain of inthomycins.
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Produtos Biológicos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Sedimentos Geológicos/microbiologia , Oxazóis/metabolismo , Streptomyces/isolamento & purificação , Streptomyces/metabolismo , Meios de Cultura/química , Meios de Cultura/metabolismo , Streptomyces/genética , Streptomyces/crescimento & desenvolvimentoRESUMO
Marine actinobacteria continue to be a rich source for the discovery of structurally diverse secondary metabolites. Here we present a new hydroxymate siderophore produced by Amycolatopsis albispora, a recently described species of this less explored actinomycete genus. Strain WP1T was isolated from sediments collected at -2945 m in the Indian Ocean. The new siderophore, designated albisporachelin, was isolated from iron depleted culture broths and the structure was established by 1D and 2D NMR and MS/MS experiments, and application of a modified Marfey's method. Albisporachelin is composed of one N-methylated-formylated/hydroxylated l-ornithine (N-Me-fh-l-Orn), one l-serine (l-Ser), one formylated/hydroxylated l-ornithine (fh-l-Orn) and a cyclo-N-methylated-hydroxylated l-ornithine (cyclo-N-Me-h-l-Orn).
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Actinomycetales/química , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiologia , Ácidos Hidroxâmicos/química , Lipídeos/química , Ornitina/análogos & derivados , Água do Mar/microbiologia , Sideróforos/química , Oceano Índico , Ferro/química , Ornitina/químicaRESUMO
Olea europaea leaves are the major byproduct of olive farming. In this study, ultrasound-assisted extraction of flavonoids from olive leaves was optimized using response surface methodology, and the flavonoid compounds and their antioxidant and anticancer activities were investigated by high performance liquid chromatography. The results showed that the optimized conditions for achieving the maximum yield of flavonoids (74.95 mg RE/g dm) were 50 °C temperature, 270 W power, 50 min time, and 41 mL/g liquid-solid ratio. There was a significant difference in the total flavonoid content between the aged and young leaves harvested in April and July, and six main components were quantified. Among them, luteolin-4'-O-glucoside was the most predominant flavonoid compound, followed by apigenin-7-O-glucoside and rutin. Olive leaves also contained small amounts of luteolin, apigenin, and quercetin. Additionally, excellent antioxidant activity was exhibited when tested with the DPPH assay; superoxide radical-scavenging ability and reducing power was also tested. The anticancer activity of the flavonoids was assessed using HeLa cervical cancer cells, and it was observed that increasing concentrations of olive leaf flavonoids resulted in decreased cancer cell viability. These results suggest that the flavonoids from olive leaves could be used as a potential source of natural antioxidants for the pharmaceutical and food industries.
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Antineoplásicos Fitogênicos , Antioxidantes , Flavonoides , Neoplasias/tratamento farmacológico , Olea/química , Folhas de Planta/química , Ondas Ultrassônicas , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
According to the previous results from transcriptome analysis of Ligustrum quihoui, a glycosyltransferase gene(xynzUGT) was cloned by rapid amplification of cDNA ends(RACE). The full length cDNA of xynzUGT was 1 598 bp, consisting of 66 bp 5'-UTR, 1 440 bp ORF and 92 bp 3'-UTR. The ORF encoded a 480 amino-acid protein(xynzUGT) with a molecular weight of 54 826.67 Da and isoelectric point of 5.82. The structure of enzyme was analyzed by using bioinformatics method, the results showed that the primary structure contained a highly conserved PSPG box of glycosyltransferase, the secondary structure included α helix(38%), ß sheet(12.1%) and random coil(49.9%), and tertiary structure was constructed by peptide chain folding to form two face-to-face α/ß/α domains(often referred to as a Rossmann domains), between which a substrate binding pocket is sandwiched. The phylogenetic tree analysis indicated that xynzUGT might catalyze glycosylation of phenylpropanoids, such as tyrosol. Further simulation experiment of molecular docking between enzyme and tyrosol showed that Gly138 and Ser285 located in the binding pocket interacted with tyrosol by hydrogen bonding. SDS-PAGE analysis exhibited that the prokaryotic expression system successfully expressed recombinant xynzUGT with molecular weight of 58 370.57 Da, but it exists in the form of non-soluble inclusion bodies. Using the molecular chaperone and enzyme co-expression method, the soluble expression was promoted to some extent. The above works laid the foundation for further studying on enzymatic reaction in vitro and clarifying the functional mechanism of enzyme.
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Glicosiltransferases/genética , Ligustrum/enzimologia , Proteínas de Plantas/genética , Clonagem Molecular , DNA Complementar , Ligustrum/genética , Simulação de Acoplamento Molecular , Filogenia , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
Currently, inhomogeneous distribution of Zn2+ on the surface of the Zn anode is still the essential reason for dendrite formation and unsatisfactory stability of zinc ion batteries. Given the merits of strong interaction between Sn and Zn, as well as a low nucleation barrier during Zn deposition, the combination of metallic Sn with carbon material is expected to improve the deposition of zinc ions and inhibit the growth of zinc dendrites by guiding the homogeneous plating/stripping of zinc on the electrode surface. In this article, zincophilic Sn nanoparticles with low nucleation barriers and strong interaction with Zn2+ were embedded into 3D N-doped carbon nanofibers using a simple electrostatic spinning technique. Accordingly, when serving as an artificial coating layer for the zinc metal anode, an ultrastable Sn@NCNFs@Zn||Sn@NCNFs@Zn symmetric cell can be achieved for over 3500 h with a low nucleation overpotential of 29.1 mV. Significantly, the full cell device assembled with the as-prepared anode and MnO2 cathode exhibits desirable electrochemical behaviors. Moreover, this simple method could be extended to other metal-carbon composites, and to ensure ease in scaling up as required. Such significant approach can provide an effective strategy for the design of high-performance zinc anodes.
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Background: Chronic inflammatory stimulation is a major risk factor for mild cognitive impairment. Mushroom consumption and inflammatory factors may play an important role in the pathogenesis of mild cognitive impairment. Additionally, consuming mushrooms can reduce the levels of inflammatory cytokines and preserve cognitive function. Therefore, this study aimed to investigate the relationship between mushroom consumption and serum inflammatory cytokines and mild cognitive impairment (MCI). Methods: Binary logistic regression was used to determine the relationship between mushroom consumption and MCI in 550 participants. Subsequently, mediation analysis was used to analyze the relationship between mushroom consumption, inflammatory factors, and the Montreal Cognitive assessment (MoCA) score in 248 participants. Results: Mushroom consumption was associated with MCI (odds ratio = 0.623, 95% confidence interval = 0.542-0.715, P < 0.001). The association between mushroom intake and MCI was mediated by interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP), and the MoCA score was 12.76% and 47.59%, respectively. Conclusion: A high intake of mushrooms was associated with a low risk of MCI. Serum inflammatory factors including IL-6 and hs-CRP play a partial mediating role between mushroom intake and the MoCA score, and the underlying mechanism needs to be further explored.
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Agaricales , Proteína C-Reativa , Disfunção Cognitiva , Inflamação , Humanos , Idoso , Masculino , Feminino , China , Proteína C-Reativa/metabolismo , Interleucina-6/sangue , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fatores de Risco , Estudos Transversais , População do Leste AsiáticoRESUMO
Lead hafnate (PbHfO3) has attracted a lot of renewed interest due to its potential as antiferroelectric (AFE) material for energy storage. However, its room temperature (RT) energy-storage performance has not been well established and no reports on the energy-storage feature of its high-temperature intermediate phase (IM) are available. In this work, high-quality PbHfO3 ceramics were prepared via the solid-state synthesis route. Based on high-temperature X-ray diffraction data, the IM of PbHfO3 was found to be orthorhombic, Imma space group, with antiparallel alignment of Pb2+ ions along the [001]cubic directions. The polarization-electric field (P-E) relation of PbHfO3 is displayed at RT as well as in the temperature range of the IM. A typical AFE loop revealed an optimal recoverable energy-storage density (Wrec) of 2.7 J/cm3, which is 286% higher than the reported data with an efficiency (η) of 65% at 235 kV/cm at RT. A relatively high Wrec value of 0.7 J/cm3 was found at 190 °C with an η of 89% at 65 kV/cm. These results demonstrate that PbHfO3 is a prototypical AFE from RT up to 200 °C, making it a suitable material for energy-storage applications in a wide temperature range.
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PURPOSE: To investigate the current status of oral health literacy among adult orthodontic patients and analyze its influencing factors. METHODS: Totally 163 adult orthodontic patients were recruited by convenience sampling method from November 2021 to February 2022 at the Department of Oral and Craniomaxillofacial Surgery, Center of Craniofacial Orthodontics in Shanghai Ninth People's Hospital. General information questionnaire, Chinese version of Health Literacy in Dentistry (HeLD-14), Chinese version of Self-Efficacy Scale for Self-care (SESS) and Social Support Rating Scale (SSRS) were applied. SPSS 21.0 software package was used for data analysis. RESULTS: The mean score of oral health literacy in adult orthodontic patients was (48.74±5.54), and the lowest score were obtained in concern (6.80±1.19) and support (6.40±1.59) dimensions. Multiple stepwise regression analysis showed that adult orthodontic patients' consultation self-efficacy, social support utilization, family or friends' orthodontic history and objective support were the influencing factors of oral health literacy. CONCLUSIONS: The oral health literacy in adult orthodontic patients is at a middle to high level, but concern and support literacy need to be improved. Strengthening consultation self-efficacy, objective support and utilization of social support can improve adult orthodontic patients' oral health literacy. Attention should be paid to patients who have no relatives or friends with history of orthodontic treatment.
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Letramento em Saúde , Saúde Bucal , Adulto , Humanos , China , Projetos de Pesquisa , Autoeficácia , OrtodontiaRESUMO
The plant B3 gene superfamily contains a large number of transcription factors playing a vital role in both vegetative growth and reproductive development in plants. Although several B3 genes have been well studied, molecular functions of the B3 genes in olive are largely unknown. In our study, a total of 200 B3 genes were identified in olive genome based on RNA-seq and comparative genomic analyses and further classified into five groups (i.e., REM, RAV, LAV, HSI, and ARF) based on phylogenetic analysis. Results of gene structure and motif composition analyses revealed diversified functions among these five groups of B3 genes. Results of genomic duplication and syntenic analyses indicated the gene expansion in the B3 genes. Results of gene expression based on both transcriptomics and relative expression revealed the tissue-biased expression patterns in B3 genes. The results of the comparative expression analysis of B3 genes between two olive cultivars with high and low oil contents identified several potential REM genes which may be involved in oil biosynthesis in olive. Based on the comprehensive characterization of the molecular structures and functions of B3 genes in olive genome, our study provided novel insights into the potential roles of B3 transcription factors in oil biosynthesis in olive and lays the groundwork for the functional explorations into this research field.
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Olea , Filogenia , Olea/genética , Genes de Plantas , Genômica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Azeite de OlivaRESUMO
To apply a network pharmacological approach to explore the targets and possible mechanisms of Kai Yu Zhong Yu Tang (KYZYT) in the treatment of tubal fimbria obstruction. The target information of KYZYT was extracted from TCMSP and HERB database. Genes related to tubal fimbria obstruction were searched using the GENECARD database. Target protein network maps (PPI) were drawn using string database analysis and Cytoscape 3.7.1 software. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were performed with the help of Perl language and biological program package in R language. To explore the multiple pharmacological mechanisms of action of KYZYT in the interventional treatment of tubal fimbria obstruction and to lay the foundation for further experimental validation. Through the collection and analysis of multiple databases, 355 biological targets of KYZYT were identified. 168 targets of tubal fimbria obstruction were obtained from disease database. The "drug-component" and "drug-target" networks of KYZYT were constructed, and the protein interaction network (PPI) of overlapping targets was analyzed to identify the key targets of the drug affecting the disease. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of KYZYT in the treatment of tubal fimbria obstruction. KYZYT has the characteristics of multi-component, multi-target and multi-pathway in the treatment of tubal fimbria obstruction, which provides new ideas and scientific basis for further clarification of the molecular mechanism.
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Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Mapas de Interação de Proteínas , SoftwareRESUMO
Tetragonal tungsten bronze (TTB) based oxides constitute a large family of dielectric materials which are known to exhibit complex distortions producing incommensurately modulated superstructures as well as significant local deviations from their average symmetry. The local deviations produce diffuse scattering in diffraction experiments. The structure as well as the charge dynamics of these materials are anticipated to be sensitive to defects, such as cation or oxygen vacancies. In this work, in an effort to understand how the structural and charge dynamical properties respond to these two types of vacancy defects, we have performed measurements of dielectric susceptibilities and single crystal diffraction experiments of two types of TTB materials with both 'filled' (Ba2NdFeNb4O15and Ba2PrFeNb4O15) and 'unfilled' (Sr0.5Ba0.5Nb2O6) cation sublattices. We also perform these measurements before and after oxygen annealing, which alters the oxygen vacancy concentrations. Surprisingly, we find that many of the diffuse scattering features that are present in the unfilled structure are also present in the filled structure, suggesting that the random fields and disorder that are characteristic of the unfilled structure are not responsible for many of the local structural features that are reflected in the diffuse scattering. Oxygen annealing clearly affected both color and dielectric properties, consistent with a diminishment of the oxygen vacancy concentration, but had little effect on observed diffuse patterns.
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The number of people living with Alzheimer's disease (AD) is increasing alongside with aging of the population. Systemic chronic inflammation and microbial imbalance may play an important role in the pathogenesis of AD. Inflammatory diets regulate both the host microbiomes and inflammatory status. This study aimed to explore the impact of inflammatory diets on oral-gut microbes in patients with AD and the relationship between microbes and markers of systemic inflammation. The dietary inflammatory properties and the oral and gut microorganisms were analyzed using the dietary inflammatory index (DII) and 16S RNA in 60 patients with AD. The α-diversity was not related to the DII (p > 0.05), whereas the ß-diversity was different in the oral microbiomes (R2 = 0.061, p = 0.013). In the most anti-inflammatory diet group, Prevotella and Olsenella were more abundant in oral microbiomes and Alistipes, Ruminococcus, Odoribacter, and unclassified Firmicutes were in the gut microbiomes (p < 0.05). Specific oral and gut genera were associated with interleukin-6 (IL)-6, complement 3 (C3), high-sensitivity C-reactive protein (hs-CRP), IL-1ß, IL-4, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) (p < 0.05). In conclusion, anti-inflammatory diets seem to be associated with increased abundance of beneficial microbes, and specific oral and gut microbial composition was associated with inflammatory markers.
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T cell hyporesponsiveness is crucial for the functional immune system and prevents the damage induced by alloreactive T cells in autoimmune pathology and transplantation. Here, we found low expression of PRDM1 in T cells from donor and recipients both related to the occurrence of acute graft-versus-host disease (aGVHD). Our systematic multiomics analysis found that the transcription factor PRDM1 acts as a master regulator during inducing human primary T cell hyporesponsiveness. PRDM1-overexpression in primary T cells expanded Treg cell subset and increased the expression level of FOXP3, while decreased expression had the opposite effects. Moreover, the binding motifs of key T cell function regulators, such as FOS, JUN and AP-1, were enriched in PRDM1 binding sites and that PRDM1 altered the chromatin accessibility of these regions. Multiomics analysis showed that PRDM1 directly upregulated T cell inhibitory genes such as KLF2 and KLRD1 and downregulated the T cell activation gene IL2, indicating that PRDM1 could promote a tolerant transcriptional profile. Further analysis showed that PRDM1 upregulated FOXP3 expression level directly by binding to FOXP3 upstream enhancer region and indirectly by upregulating KLF2. These results indicated that PRDM1 is sufficient for inducing human primary T cell hyporesponsiveness by transcriptomic and epigenetic manners.
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Doença Enxerto-Hospedeiro , Transcriptoma , Epigenoma , Fatores de Transcrição Forkhead/genética , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Ativação Linfocitária/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/genéticaRESUMO
Gut-liver axis and cellular homeostasis play key roles in alcohol liver disease (ALD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis. We investigated whether the beneficial effects and underlying mechanisms of Jia-ga-song Tang (JGST) against ALD were associated with gut-liver axis and cellular homeostasis. A predictive network depicting the relationship between Jia-Ga-Song-Tang (JGST) and alcoholic liver disease (ALD) was designed by Network pharmacology. Next, 5% v/v Lieber-DeCarli alcohol liquid diet was used to establish the ALD. JGST protected the liver damage, repaired the intestines to alleviate the Two-hit on the liver, and balanced the cellular homeostasis. It was manifested in repairing the liver and intestinal pathological structure, reducing serum ALT, AST, and liver TG, TC, MDA, CAT, and increasing liver GSH, and intestine GSH-Px. JGST mainly inhibited the liver mRNA levels of HO-1, NQO1, GCLC, FASN, and PPARα and activated the intestinal mRNA levels of HO-1 and NQO1, while inhibiting the liver protein levels of HO-1, NQO1. Furthermore, LPS and LBP in the plasma and the expression of inflammatory factors such as IL-1ß, TNF-α, IL-6, TGFß1, CD14, and Myd88 were reduced after treatment to prove that JGST protects the liver from Two-hit. Ethanol was used to intervene in HepG2 and IEC-6 to establish an ALD cell model and treated by Germacrone, ML385, and TBHQ. repaired the intestinal barrier, and inhibited Nrf2 in IEC-6, but protect the HepG2 by activating Nrf2 to balance cellular homeostasis. Our results reinforce that JGST provides an effective protective method for alcoholic liver disease (ALD) by regulating Gut-liver axis and cellular homeostasis.
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Objective: Alterations in the oral or gut microbiotas have been reported in patients with subjective and mild cognitive impairment or AD dementia. However, whether these microbiotas change with the severity of the AD spectrum (mild, moderate, and severe AD) remains unknown. Thus, we compared alterations in the composition and gene functions of the oral and gut microbiota between different phases of AD. Methods: We recruited 172 individuals and classified these into three groups: healthy controls (n = 40), a mild AD group (n = 43) and a moderate AD group (n = 89). Subgingival plaques and fecal samples were collected from all individuals. Then, we conducted 16S ribosomal RNA. sequencing to analyze the microbiotas. Results: In order of the severity of cognition impairment (from normal to mild and to moderate AD), the oral abundances of the phyla Firmicutes and Fusobacteria showed a gradual upwards trend, while the abundance of the Proteobacteria phylum gradually decreased. In contrast, the abundance of the Firmicutes and Bacteroidetes phyla in the gut decreased progressively, while that of the Proteobacteria, Verrucomicrobia and Actinobacteria phyla increased gradually. Key differences were identified in the microbiomes when compared between the mild AD and moderate AD groups when applying the linear discriminant analysis effect size (LEfSe) algorithm. LEfSe analysis revealed alterations that were similar to those described above; furthermore, different bacterial taxa were associated with MMSE scores and age. KEGG analysis showed that the functional pathways associated with the oral microbiota were mainly involved in membrane transport and carbohydrate metabolism, while the gene functions of the fecal microbiota related to metabolism of amino acids, energy, cofactors and vitamins; identified significant differences among the three groups. Venn diagram analysis revealed that the number of genera that were present in both the oral and gut microbiota increased progressively from NC to mild AD and then to moderate AD. Conclusions: This study is the first to report a comparative analysis of the oral and fecal microbiota of patients with mild and moderate AD. The compositions and functions of the oral and gut microbiotas differed when compared between different stages of AD.