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1.
Cell ; 145(6): 875-89, 2011 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-21663792

RESUMO

Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to a differentiated cell state. Here, we asked how mouse embryonic stem cells (ESCs) leave the pluripotent state and choose between germ layer fates. By analyzing the dynamics of the transcriptional circuit that maintains pluripotency, we found that Oct4 and Sox2, proteins that maintain ESC identity, also orchestrate germ layer fate selection. Oct4 suppresses neural ectodermal differentiation and promotes mesendodermal differentiation; Sox2 inhibits mesendodermal differentiation and promotes neural ectodermal differentiation. Differentiation signals continuously and asymmetrically modulate Oct4 and Sox2 protein levels, altering their binding pattern in the genome, and leading to cell fate choice. The same factors that maintain pluripotency thus also integrate external signals and control lineage selection. Our study provides a framework for understanding how complex transcription factor networks control cell fate decisions in progenitor cells.


Assuntos
Diferenciação Celular , Células-Tronco Embrionárias/citologia , Regulação da Expressão Gênica no Desenvolvimento , Camadas Germinativas/citologia , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Animais , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Homeodomínio/metabolismo , Camundongos , Proteína Homeobox Nanog , Células-Tronco Pluripotentes/citologia
2.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38216523

RESUMO

Perceiving and modulating emotions is vital for cognitive function and is often impaired in neuropsychiatric conditions. Current tools for evaluating emotional dysregulation suffer from subjectivity and lack of precision, especially when it comes to understanding emotion from a regulatory or control-based perspective. To address these limitations, this study leverages an advanced methodology known as functional brain controllability analysis. We simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data from 17 healthy subjects engaged in emotion processing and regulation tasks. We then employed a novel EEG/fMRI integration technique to reconstruct cortical activity in a high spatiotemporal resolution manner. Subsequently, we conducted functional brain controllability analysis to explore the neural network control patterns underlying different emotion conditions. Our findings demonstrated that the dorsolateral and ventrolateral prefrontal cortex exhibited increased controllability during the processing and regulation of negative emotions compared to processing of neutral emotion. Besides, the anterior cingulate cortex was notably more active in managing negative emotion than in either controlling neutral emotion or regulating negative emotion. Finally, the posterior parietal cortex emerged as a central network controller for the regulation of negative emotion. This study offers valuable insights into the cortical control mechanisms that support emotion perception and regulation.


Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Emoções/fisiologia , Cognição/fisiologia , Transtornos do Humor , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal
3.
Mol Pharm ; 21(6): 2922-2936, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38751169

RESUMO

With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to H2O2, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.


Assuntos
Lipogênese , Fígado , Camundongos Endogâmicos C57BL , Nanopartículas , Hepatopatia Gordurosa não Alcoólica , Espécies Reativas de Oxigênio , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Nanopartículas/química , Lipogênese/efeitos dos fármacos , Masculino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Receptores Notch/metabolismo , Receptores Notch/antagonistas & inibidores , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Bilirrubina , Polietilenoglicóis/química , Modelos Animais de Doenças , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Dibenzazepinas
4.
Mol Breed ; 44(7): 45, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38911334

RESUMO

The brown planthopper (Nilaparvata lugens Stål, BPH) is the most destructive pest of rice (Oryza sativa L.). Utilizing resistant rice cultivars that harbor resistance gene/s is an effective strategy for integrated pest management. Due to the co-evolution of BPH and rice, a single resistance gene may fail because of changes in the virulent BPH population. Thus, it is urgent to explore and map novel BPH resistance genes in rice germplasm. Previously, an indica landrace from India, Paedai kalibungga (PK), demonstrated high resistance to BPH in both in Wuhan and Fuzhou, China. To map BPH resistance genes from PK, a BC1F2:3 population derived from crosses of PK and a susceptible parent, Zhenshan 97 (ZS97), was developed and evaluated for BPH resistance. A novel BPH resistance locus, BPH39, was mapped on the short arm of rice chromosome 6 using next-generation sequencing-based bulked segregant analysis (BSA-seq). BPH39 was validated using flanking markers within the locus. Furthermore, near-isogenic lines carrying BPH39 (NIL-BPH39) were developed in the ZS97 background. NIL-BPH39 exhibited the physiological mechanisms of antibiosis and preference toward BPH. BPH39 was finally delimited to an interval of 84 Kb ranging from 1.07 to 1.15 Mb. Six candidate genes were identified in this region. Two of them (LOC_Os06g02930 and LOC_Os06g03030) encode proteins with a similar short consensus repeat (SCR) domain, which displayed many variations leading to amino acid substitutions and showed higher expression levels in NIL-BPH39. Thus, these two genes are considered reliable candidate genes for BPH39. Additionally, transcriptome sequencing, DEGs analysis, and gene RT-qPCR verification preliminary revealed that BPH39 may be involved in the jasmonic acid (JA) signaling pathway, thus mediating the molecular mechanism of BPH resistance. This work will facilitate map-based cloning and marker-assisted selection for the locus in breeding programs targeting BPH resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01485-6.

5.
J Sci Food Agric ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567792

RESUMO

BACKGROUND: This study explored the denaturation of 11S globulin, a protein known for its diverse functional properties in soy protein applications, at pH 3.0 and pH 10.0, followed by a gradual return to pH 7.0 to facilitate renaturation. It investigated the structural and functional changes during renaturation induced by a change in pH, revealing the stabilization mechanism of 11S globulin. RESULTS: The findings revealed that during pH adjustment to neutral, the denatured soybean 11S globulin - resulting from alkaline (pH 10.0) or acidic (pH 3.0) treatments - experienced a refolding of its extended tertiary structure to varying extents. The particle size and the proportions of α-helix and ß-sheet in the secondary structure aligned progressively with those of the natural-state protein. However, for the alkali-denatured 11S, the ß-sheet content decreased upon adjustment to neutral, whereas an increase was observed for the acid-denatured 11S. In terms of functional properties, after alkaline denaturation, the foaming capacity (FC) and emulsifying activity index (EAI) of 11S increased by 1.4 and 1.2 times, respectively, in comparison with its native state. The solubility, foamability, and emulsifiability of the alkali-denatured 11S gradually diminished during renaturation but remained superior to those of the native state. Conversely, these properties showed an initial decline, followed by an increase during renaturation triggered by pH neutralization. CONCLUSIONS: This research contributes to the enhancement of protein functionality, offering a theoretical foundation for the development of functional soy protein products and expanding their potential applications. © 2024 Society of Chemical Industry.

6.
Am J Orthod Dentofacial Orthop ; 166(1): 81-91, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38661622

RESUMO

INTRODUCTION: This study aimed to perform a bibliometric analysis examining contributing countries and collaborative networks, authors and collaborative relationships, the performance of the institutions, and cocited journals and references in 3 major orthodontic journals (American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, and Angle Orthodontist) over two 10-year periods (2002-2011 and 2012-2021). METHODS: In this study, 4432 publications in the first decade and 4012 publications in the second decade were quantitatively analyzed and visualized using visualization software such as VOSviewer (Leiden University, Leiden, Netherlands), CiteSpace (Drexel University, Philadelphia, Pa), and Scimago Graphica (SCImago Lab, Spain). RESULTS: Institutions in the United States had the highest number of publications through the 2 decades, whereas Brazil, South Korea, and China achieved significant improvements in performance in the second decade compared with the first. Closer collaborative networks among scholars were revealed in the second decade. The cocitation analysis of the journals showed that highly cited journals included more professional orthodontic journals in the second decade than in the first decade. CONCLUSIONS: Bibliometric analysis of publications in 3 major orthodontic journals over two 10-year periods revealed a trend of diversification in countries and institutions participating in publishing, international collaborations, and collaboration networks among authors in the field of orthodontics during the 2 decades.


Assuntos
Bibliometria , Ortodontia , Publicações Periódicas como Assunto , Ortodontia/estatística & dados numéricos , Publicações Periódicas como Assunto/estatística & dados numéricos , Humanos , Editoração/estatística & dados numéricos , Fatores de Tempo
7.
Am J Orthod Dentofacial Orthop ; 165(4): 471-487, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38276931

RESUMO

INTRODUCTION: In many evidence-based approaches to orthodontic research, randomized controlled trials (RCTs) represent authoritative evidence to identify rational therapeutics. This study aimed to perform mappings of bibliometric networks on orthodontic RCTs and summarize visual characteristics between 1991 and 2022. METHODS: The articles were retrieved from the Web of Science Core Collection in October 2022 without an initial time limit. Only orthodontic RCTs were eligible. Some bibliometric tools (HistCite, VOSviewer, SCImago Graphica, and CiteSpace) were applied for visualized analysis. Data such as geography, productive institutions, hot articles, journals, authors, references, and keywords were extracted and summarized for analysis. RESULTS: A total of 1122 orthodontic RCTs were searched. A total of 3841 authors from 1157 institutions in 65 countries published orthodontic RCTs. The United States (149) was the most prolific country, and the University of Sao Paulo (35) was the most productive institution. The American Journal of Orthodontics and Dentofacial Orthopedics (206) was the most popular journal for scholars. The visualization results of keyword co-occurrence identified 5 clusters: (1) tooth movement and auxiliary measures, (2) appliances and oral health, (3) orthodontic discomfort and symptomatic therapy, (4) periodontal disease in orthodontics and health maintenance, and (5) retention and relapse. CONCLUSIONS: Over the past 31 years, publications and citations on orthodontic RCTs from the Web of Science Core Collection have increased notably across many countries, authors, and institutions. Recently, there has been a significant increase in the attention to orthodontic RCTs that focus on accelerating tooth movement.


Assuntos
Assistência Odontológica , Ortopedia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Saúde Bucal , Bibliometria
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 224-229, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322535

RESUMO

Jawbone injuries resulting from trauma, diseases, and surgical resections are commonly seen in clinical practice, necessitating precise and effective strategies for repair and reconstruction to restore both function and aesthetics. The precise and effective repair and the reconstruction of jawbone injuries pose a significant challenge in the field of oral and maxillofacial surgery, owing to the unique biomechanical characteristics and physiological functions of the jawbone. The natural repair process following jawbone injuries involves stages such as hematoma formation, inflammatory response, ossification, and bone remodeling. Bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-ß), vascular endothelial growth factor (VEGF), and other growth factors play crucial roles in promoting jawbone regeneration. Cytokines such as interleukins and tumor necrosis factor play dual roles in regulating inflammatory response and bone repair. In recent years, significant progress in molecular biology research has been made in the field of jawbone repair and reconstruction. Tissue engineering technologies, including stem cell therapy, bioactive scaffolds, and growth factor delivery systems, have found important applications in jawbone repair. However, the intricate molecular regulatory mechanisms involved in the complex jawbone repair and reconstruction methods are not fully understood and still require further research. Future research directions will be focused on the precise control of these molecular processes and the development of more efficient combination therapeutic strategies to promote the effective and functional reconstruction of the jawbone. This review aims to examine the latest findings on the molecular regulatory mechanisms of the repair and reconstruction of jawbone injuries and the therapeutic strategies. The conclusions drawn in this article provide a molecular-level understanding of the repair of jawbone injuries and highlight potential directions for future research.


Assuntos
Osteogênese , Fator A de Crescimento do Endotélio Vascular , Remodelação Óssea , Peptídeos e Proteínas de Sinalização Intercelular , Engenharia Tecidual , Fator de Crescimento Transformador beta , Humanos
9.
J Biol Chem ; 298(5): 101853, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35331738

RESUMO

There is growing evidence that mammalian cells deploy a mitochondria-associated metabolon called the purinosome to perform channeled de novo purine biosynthesis (DNPB). However, the molecular mechanisms of this substrate-channeling pathway are not well defined. Here, we present molecular evidence of protein-protein interactions (PPIs) between the human bifunctional phosphoribosylaminoimidazole carboxylase/succinocarboxamide synthetase (PAICS) and other known DNPB enzymes. We employed two orthogonal approaches: bimolecular fluorescence complementation, to probe PPIs inside live, intact cells, and co-immunoprecipitation using StrepTag-labeled PAICS that was reintegrated into the genome of PAICS-knockout HeLa cells (crPAICS). With the exception of amidophosphoribosyltransferase, the first enzyme of the DNPB pathway, we discovered PAICS interacts with all other known DNPB enzymes and with MTHFD1, an enzyme which supplies the 10-formyltetrahydrofolate cofactor essential for DNPB. We show these interactions are present in cells grown in both purine-depleted and purine-rich conditions, suggesting at least a partial assembly of these enzymes may be present regardless of the activity of the DNPB pathway. We also demonstrate that tagging of PAICS on its C terminus disrupts these interactions and that this disruption is correlated with disturbed DNPB activity. Finally, we show that crPAICS cells with reintegrated N-terminally tagged PAICS regained effective DNPB with metabolic signatures of channeled synthesis, whereas crPAICS cells that reintegrated C-terminally tagged PAICS exhibit reduced DNPB intermediate pools and a perturbed partitioning of inosine monophosphate into AMP and GMP. Our results provide molecular evidence in support of purinosomes and suggest perturbing PPIs between DNPB enzymes negatively impact metabolite flux through this important pathway.


Assuntos
Peptídeo Sintases , Purinas , Humanos , Amidofosforribosiltransferase , Células HeLa , Peptídeo Sintases/metabolismo , Purinas/biossíntese
10.
Chemistry ; 29(29): e202204071, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-36879435

RESUMO

Ceria nanoparticles (CNPs) are important typical nanozymes with multiple enzyme mimetic activities, which could facilitate the oxidation of organic dyes in acidic conditions, because of the oxidase mimetic activity. Usually, the regulation of oxidase mimetic activity is focused on the adjustment of the structure, morphology, composition, surface, and other factors of nanozymes. However, the influence of the surrounding environment is not considered, which is very important during the reaction process. In this work, the oxidase mimetic activity of CNPs in buffer solutions including citric acid, acetic acid and glycine buffer solutions was investigated, with the results that carboxyl group in buffer solution could adsorb the CNPs on the surface to promote the oxidase mimetic activity. Due to the chelation with the cerium ion, the enhancement is more significant by molecules with polycarboxylic groups, and the enhancement is more efficient by carboxyl molecules in buffer solution, compared with the modification of the carboxyl groups on the surface, because of easier operation and smaller steric hindrance. From the viewpoint of increasing the oxidase mimetic activity of CNPs, the work is expected to provide references for the selection of the reaction systems to optimize the oxidase mimetic activity in bio-detection applications.


Assuntos
Cério , Nanopartículas , Oxirredutases/metabolismo , Nanopartículas/química , Oxirredução , Cério/química , Quelantes
11.
Virus Genes ; 59(2): 290-300, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36607487

RESUMO

A lysogenic phage vB_EcoP_DE5 (hereafter designated DE5) was isolated from donkey-derived Escherichia coli. The bacteriophage was examined by transmission electron microscopy, and the result showed that DE5 belonged to the genus Kuravirus. DE5 was sensitive to changes in temperature and pH, and it could maintain its activity at pH 7 and below 60 â„ƒ. The whole genome sequencing revealed that DE5 had a double-stranded DNA genome of 77, 305 bp with 42.09% G+C content. A total of 126 open reading frames (ORFs) were identified, including functional genes related to phage integration, DNA replication and modification, transcriptional regulation, structural and packaging proteins, and host cell lysis. One phage integrase gene, one autotransporter adhesin gene, and one tRNA gene were predicted in the whole genome, and no genes associated with drug resistance were identified. The phage DE5 integrase contained 187 amino acids and belonged to the small serine recombinase family. BLASTn analysis revealed that phage DE5 had a high-sequence identity (96%) with E. coli phage SU10. Phylogenetic analysis showed that phage DE5 was a member of the genus Kuravirus. The whole genome sequencing of lysogenic phage DE5 enhanced our understanding of lysogenic phages and their therapeutic applications.


Assuntos
Bacteriófagos , Podoviridae , Bacteriófagos/genética , Escherichia coli/genética , Filogenia , Genoma Viral , Podoviridae/genética , Sequenciamento Completo do Genoma , Integrases/genética , Fases de Leitura Aberta
12.
Virus Genes ; 59(5): 752-762, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37322310

RESUMO

Bacteriophages are an important source of novel genetic diversity. Sequencing of phage genomes can reveal new proteins with potential uses in phage therapy and help unravel the diversity of biological mechanisms by which phages take over the machinery of the host during infection. To expand the available collection of phage genomes, we have isolated, sequenced, and assembled the genome sequences of three phages that infect three pathogenic Escherichia coli strains: vB_EcoM_DE15, vB_EcoM_DE16, and vB_EcoM_DE17. Morphological characterization and genomic analysis indicated that all three phages were strictly lytic and free from integrases, virulence factors, toxins, and antimicrobial resistance genes. All three phages contained tRNAs, and especially, vB_EcoM_DE17 contained 25 tRNAs. The genomic features of these phages indicate that natural phages are capable of lysing pathogenic E.coli and have great potential in the biocontrol of bacteria.


Assuntos
Bacteriófagos , Bacteriófagos/genética , Escherichia coli/genética , Genoma Viral , Genômica , Bactérias
13.
Int J Clin Pract ; 2023: 1489905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497125

RESUMO

Objective: In this study, we aimed to explore the efficacy of the autologous platelet-rich plasma (PRP) interventional circulatory perfusion combined with radiofrequency ablation and thermocoagulation (RFAT) in the treatment of discogenic low back pain (DLBP). Methods: From January 2020 to November 2022, 158 patients of the Second Affiliated Hospital of Nanchang University were selected as the study subjects, and 24 patients met the exclusion criteria. The 134 patients who met the inclusion criteria were divided into 65 patients in the control group (3 patients lost to follow-up) and 69 patients in the observation group (5 patients lost to follow-up), so 126 patients were actually completed the study, including 62 patients in the control group and 64 patients in the observation group. The control group responsible disc received RFAT, and an interventional circulatory perfusion was performed; the observation group received RFAT, and an interventional circulatory perfusion was performed, and then autologous PRP 2 ml was injected. Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were performed before and 4 and 8 weeks after treatment, and the efficacy was evaluated at 4 and 8 weeks after treatment. The changes of lumbar disc MRI before and after treatment were observed. Results: The differences in the Visual Analog Scale (VAS) scores and the Oswestry Disability Index (ODI) between the observation group and the control group before the treatment were not statistically significant (P > 0.05 in both). However, four weeks and eight weeks after the treatment, the VAS scores and the ODIs were significantly lower in both groups than those before the treatment (P < 0.05 in both). In terms of the therapeutic efficacy, eight weeks after the treatment, the total effective rates in the control group and the observation group were 67.7% and 87.5%, respectively, with the observation group being superior to the control group (P < 0.05). Conclusion: After RFAT, interventional circulatory perfusion combined with autologous PRP intramedullary injection in the lumbar disc is a safe and effective treatment for DLBP, and it had superior long-term effects in improving the clinical symptoms and patient dysfunction than the RFAT and interventional circulatory perfusion.


Assuntos
Dor Lombar , Plasma Rico em Plaquetas , Ablação por Radiofrequência , Humanos , Dor Lombar/terapia , Resultado do Tratamento , Eletrocoagulação , Perfusão , Vértebras Lombares/cirurgia
14.
Caries Res ; 57(1): 32-42, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36634644

RESUMO

This study aimed to review the current state of the root caries field, explore the current hot topic, and anticipate future research frontiers. The Web of Science Core Collections was searched to acquire publications that were relevant to root caries from 1992 to 2021. After retrieval and manual screening, the co-occurrence and co-operation analysis of keywords and countries/institutions/authors were performed through CiteSpace and VOSviewer based on two periods (1992-2006 and 2007-2021). From 1992 to 2021, 451 unique publications were selected. The USA, which has been the center of international cooperation, has produced the most publications in the research area in 1992-2021. Journal of Dental Research and Caries Research are the main counterpart journals in the field of root caries. The University of London is the institution with the highest number of publications in the analyzed 30 years. "Demineralization," "remineralization," "aged," "dentin," and "fluoride" have been commonly used as keywords throughout the past 30 years. More studies from different aspects have been published in the field of root caries in recent years (2007-2021). The findings of this study provide a full picture of the last 30 years in this research area; hopefully, they also provide essential information for researchers and policymakers to make decisions.


Assuntos
Cárie Dentária , Cárie Radicular , Humanos , Idoso , Bibliometria , Assistência Odontológica , Fluoretos
15.
Mediators Inflamm ; 2023: 6645476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37114236

RESUMO

It is difficult for traditional therapies to further improve the prognosis of hepatocellular carcinoma (LIHC), and immunotherapy is considered to be a promising approach to overcome this dilemma. However, only a minority of patients benefit from immunotherapy, which greatly limits its application. Therefore, it is particularly urgent to elucidate the specific regulatory mechanism of tumor immunity so as to provide a new direction for immunotherapy. NOP2/Sun RNA methyltransferase 3 (NSUN3) is a protein with RNA binding and methyltransferase activity, which has been shown to be involved in the occurrence and development of a variety of tumors. At present, the relationship between NSUN3 and immune implication in LIHC has not been reported. In this study, we first revealed that NSUN3 expression is upregulated in LIHC and that patients with high NSUN3 expression have a poor prognosis through multiple databases. Pathway enrichment analysis demonstrated that NSUN3 may be participated in cell adhesion and cell matrix remodeling. Next, we obtained a set of genes coexpressed with NSUN3 (NCGs). Further LASSO regression was performed based on NCGs, and a risk score model was constructed, which proved to have good predictive power. In addition, Cox regression analysis revealed that the risk score of NCGs model was an independent risk factor for LIHC patients. Moreover, we established a nomogram based on the NCGs-related model, which was verified to have a good predictive ability for the prognosis of LIHC. Furthermore, we investigated the relationship between NCGs-related model and immune implication. The results implied that our model was closely related to immune score, immune cell infiltration, immunotherapy response, and multiple immune checkpoints. Finally, the pathway enrichment analysis of NCGs-related model showed that the model may be involved in the regulation of various immune pathways. In conclusion, our study revealed a novel role of NSUN3 in LIHC. The NSUN3-based prognostic model may be a promising biomarker for inspecting the prognosis and immunotherapy response of LIHC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Prognóstico , Neoplasias Hepáticas/terapia , Imunoterapia , Metiltransferases , RNA
16.
Acta Biochim Biophys Sin (Shanghai) ; 55(3): 331-342, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36786073

RESUMO

Antitumour treatments are evolving, including bacteria-mediated cancer therapy which is concurrently an ancient and cutting-edge approach. Salmonella typhimurium is a widely studied bacterial species that colonizes tumor tissues, showing oncolytic and immune system-regulating properties. It can be used as a delivery vector for genes and drugs, supporting conventional treatments that lack tumor-targeting abilities. This article summarizes recent evidence on the anticancer mechanisms of S. typhimurium alone and in combination with other anticancer treatments, suggesting that it may be a suitable approach to disease management.


Assuntos
Neoplasias , Salmonella typhimurium , Humanos , Salmonella typhimurium/genética , Neoplasias/terapia , Bactérias
17.
Proc Natl Acad Sci U S A ; 117(27): 16009-16018, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571913

RESUMO

Food and drug products contain diverse and abundant small-molecule additives (excipients) with unclear impacts on human physiology, drug safety, and response. Here, we evaluate their potential impact on intestinal drug absorption. By screening 136 unique compounds for inhibition of the key intestinal transporter OATP2B1 we identified and validated 24 potent OATP2B1 inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or noninhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R-N=N-R') dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient and a potent inhibitor of OATP2B1, decreased the plasma level of the OATP2B1 substrate fexofenadine, suggesting that FD&C Red No. 40 has the potential to block drug absorption through OATP2B1 inhibition in vivo. However, the gut microbiomes of multiple unrelated healthy individuals as well as diverse human gut bacterial isolates were capable of inactivating the identified azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine and provide a framework for the data-driven selection of excipients. Furthermore, the ubiquity and genetic diversity of gut bacterial azoreductases coupled to experiments in conventionally raised and gnotobiotic mice suggest that variations in gut microbial community structure may be less important to consider relative to the high concentrations of azo dyes in food products, which have the potential to saturate gut bacterial enzymatic activity.


Assuntos
Bactérias/metabolismo , Excipientes/metabolismo , Aditivos Alimentares/metabolismo , Alimentos , Microbioma Gastrointestinal/fisiologia , Absorção Intestinal/fisiologia , Transportadores de Ânions Orgânicos/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Antialérgicos/metabolismo , Antialérgicos/farmacocinética , Compostos Azo , Bactérias/isolamento & purificação , Excipientes/farmacocinética , Feminino , Aditivos Alimentares/farmacocinética , Antagonistas não Sedativos dos Receptores H1 da Histamina/metabolismo , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacocinética , Humanos , Absorção Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Terfenadina/análogos & derivados , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
18.
Clin Oral Investig ; 28(1): 11, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38129367

RESUMO

OBJECTIVES: The aim of this study was to evaluate the effects of Hiflow with other two kinds of root canal sealers on the biological behavior of stem cells from the apical papilla (SCAP), the influence on inflammatory cytokines release and its antibacterial effects. MATERIALS AND METHODS: Material extracts of Hiflow, iRoot SP, and AH Plus were prepared. Then, SCAP was incubated with extracts. The effects were evaluated by CCK-8, wound healing assay, ALP staining, alizarin red staining, and qRT-PCR. Meanwhile, polymorphonuclears (PMNs) and monocytes were isolated and treated with extracts for 4 h and 24 h respectively. Cell viability was analyzed by Annexin-V/PI double staining flow cytometry. The effects on the release of cytokines were observed by ELISA. The antibacterial effects of different sealers were tested against three kinds of bacteria found in chronic apical periodontitis. RESULTS: A series of results of SCAP showed that Hiflow and iRoot SP could promote cell proliferation, migration, and osteogenesis (p < 0.05). Although Hiflow was associated with greater cell apoptosis and necrosis when incubated with PMNs and monocytes (p < 0.05), it had an approximate release of anti-inflammatory cytokines with iRoot SP, which was higher than AH plus (p < 0.05). The co-culture showed that Hiflow and iRoot SP inhibited the colony formation of F. nucleatum (p < 0.05). However, both sealers had no obvious antibacterial effect on E. faecalis and P. gingivalis (p > 0.05). CONCLUSIONS: In summary, Hiflow and iRoot SP both had positive biological stimulus on SCAP. Meanwhile, Hiflow showed a better induction on anti-inflammatory cytokines over the others. All the properties mentioned above and its antibacterial effect of F. nucleatum promise Hiflow a bright application prospect in endodontic uses. CLINICAL RELEVANCE: References for clinical work to use BC Sealer Hiflow as a good biological root canal sealer.


Assuntos
Cavidade Pulpar , Materiais Restauradores do Canal Radicular , Materiais Restauradores do Canal Radicular/farmacologia , Silicatos/farmacologia , Antibacterianos/farmacologia , Citocinas , Anti-Inflamatórios , Resinas Epóxi , Teste de Materiais
19.
Int J Mol Sci ; 24(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36835606

RESUMO

Clostridium perfringens (C. perfringens) is one of the foremost pathogens responsible for diarrhea in foals. As antibiotic resistance increases, phages that specifically lyse bacteria are of great interest to us with regard to C. perfringens. In this study, a novel C. perfringens phage DCp1 was isolated from the sewage of a donkey farm. Phage DCp1 had a non-contractile short tail (40 nm in length) and a regular icosahedral head (46 nm in diameter). Whole-genome sequencing indicated that phage DCp1 had a linear double-stranded DNA genome with a total length of 18,555 bp and a G + C content of 28.2%. A total of 25 ORFs were identified in the genome, 6 of which had been assigned to functional genes, others were annotated to encode hypothetical proteins. The genome of phage DCp1 lacked any tRNA, virulence gene, drug resistance gene, or lysogenic gene. Phylogenetic analysis indicated that phage DCp1 belonged to the family Guelinviridae, Susfortunavirus. Biofilm assay showed that phage DCp1 was effective in inhibiting the formation of C. perfringens D22 biofilms. Phage DCp1 could completely degrade the biofilm after 5 h of interaction. The current study provides some basic information for further research on phage DCp1 and its application.


Assuntos
Bacteriófagos , Animais , Cavalos/genética , Bacteriófagos/genética , Clostridium perfringens , Filogenia , Genoma Viral , Genômica , Biofilmes
20.
Langmuir ; 38(31): 9587-9596, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35881583

RESUMO

The advanced oxidation process of the photo-Fenton reaction can produce hydroxyl radicals with extremely strong oxidizing properties for the efficient and green degradation of various chemical and microbial pollutants. Herein, we report an approach to fabricating heterogeneous Fenton catalysts of ß-FeOOH nanorods on porous substrates triggered by mussel-inspired coatings of levodopa (3,4-dihydroxy-phenyl-l-alanine, l-DOPA) and polyethylenimine (PEI) for efficient photocatalytic dyes' degradation and sterilization. The l-DOPA-based coatings not only promote the formation and immobilization of ß-FeOOH nanorods on the porous substrates by strong coordination between catechol/carboxyl groups and Fe3+ but also improve the energy band structure of the Fenton catalysts through a valence band blue shift and band gap narrowing. The photo-Fenton catalysts prepared by the l-DOPA-based coatings exhibit high electron transport efficiency and improved utilization of sunlight. Only 2 h of mineralization is needed to fabricate these catalysts with excellent photocatalytic efficiency, in which the degradation efficiency of methylene blue can reach 99% within 30 min, whereas the sterilization efficiency of E. coli/S. aureus can reach 93%/94% within 20 min of the photo-Fenton reaction. Additionally, the prepared catalysts reveal a high photodegradation performance for various dyes including methylene blue, methyl blue, methyl orange, direct yellow, and rhodamine B. Furthermore, the catalysts retain high dye degradation efficiencies of above 90% after five photodegradation cycles, indicating cycling performance and good stability.


Assuntos
Corantes , Levodopa , Corantes/química , Escherichia coli , Peróxido de Hidrogênio/química , Ferro/química , Azul de Metileno , Porosidade , Staphylococcus aureus , Esterilização
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