Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
J Am Chem Soc ; 146(19): 13438-13444, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38687695

RESUMO

The Baeyer-Villiger oxidation of ketones is a crucial oxygen atom transfer (OAT) process used for ester production. Traditionally, Baeyer-Villiger oxidation is accomplished by thermally oxidizing the OAT from stoichiometric peroxides, which are often difficult to handle. Electrochemical methods hold promise for breaking the limitation of using water as the oxygen atom source. Nevertheless, existing demonstrations of electrochemical Baeyer-Villiger oxidation face the challenges of low selectivity. We report in this study a strategy to overcome this challenge. By employing a well-known water oxidation catalyst, Fe2O3, we achieved nearly perfect selectivity for the electrochemical Baeyer-Villiger oxidation of cyclohexanone. Mechanistic studies suggest that it is essential to produce surface hydroperoxo intermediates (M-OOH, where M represents a metal center) that promote the nucleophilic attack on ketone substrates. By confining the reactions to the catalyst surfaces, competing reactions (e.g., dehydrogenation, carboxylic acid cation rearrangements, and hydroxylation) are greatly limited, thereby offering high selectivity. The surface-initiated nature of the reaction is confirmed by kinetic studies and spectroelectrochemical characterizations. This discovery adds nucleophilic oxidation to the toolbox of electrochemical organic synthesis.

2.
Biochem Biophys Res Commun ; 700: 149535, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38308909

RESUMO

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.


Assuntos
Doença da Artéria Coronariana , Circulação Coronária , Coelhos , Animais , Microcirculação , Circulação Coronária/fisiologia , Miocárdio/patologia
3.
Toxicol Appl Pharmacol ; 486: 116952, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38705399

RESUMO

The incidence of contrast-induced acute kidney injury (CI-AKI) has escalated to become the third most prevalent cause of hospital-acquired AKI, with a lack of efficacious interventions. Berberine (BBR) possesses diverse pharmacological effects and exhibits renoprotective properties; however, limited knowledge exists regarding its impact on CI-AKI. Therefore, our study aimed to investigate the protective effects and underlying mechanisms of BBR on CI-AKI in a mice model, focusing on the nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3) inflammasome and mitophagy. The CI-AKI mice model was established by administering NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg), indomethacin (10 mg/kg), and iohexol (11 g/kg) following water deprivation. A pretreatment of 100 mg/kg of BBR was orally administered to the mice for two weeks. Renal injury markers, damage-associated molecular patterns (DAMPs), renal histopathology, mitochondrial morphology, autophagosomes, and potential mechanisms were investigated. BBR effectively reduced levels of renal injury biomarkers such as serum cystatin C, urea nitrogen, and creatinine, downregulated the protein level of kidney injury molecule 1 (KIM1), and mitigated renal histomorphological damage. Moreover, BBR reduced DAMPs, including high mobility group box-1 (HMGB1), heat shock protein 70 (HSP70), and uric acid (UA). It also alleviated oxidative stress and inflammatory factors such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß). Furthermore, the activation of NLRP3 inflammasome was attenuated in the BBR pretreatment group, as evidenced by both mRNA and protein levels. Electron microscopy and western blotting examination revealed that BBR mitigated mitochondrial damage and enhanced mitophagy. Additionally, BBR increased the P-AMPK/AMPK ratio. These findings indicated that BBR exerted a protective effect against CI-AKI by suppressing NLRP3 inflammasome activation and modulating mitophagy, providing a potential therapeutic strategy for its prevention.


Assuntos
Injúria Renal Aguda , Berberina , Meios de Contraste , Modelos Animais de Doenças , Inflamassomos , Mitofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Masculino , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Berberina/farmacologia , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Camundongos Endogâmicos C57BL , Mitofagia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
4.
Cell Biol Toxicol ; 40(1): 34, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38769159

RESUMO

Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development.


Assuntos
Malformações Anorretais , Redes Reguladoras de Genes , Transdução de Sinais , Transcriptoma , Animais , Malformações Anorretais/genética , Malformações Anorretais/metabolismo , Malformações Anorretais/embriologia , Transdução de Sinais/genética , Transcriptoma/genética , Ratos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Gravidez , Embrião de Mamíferos/metabolismo , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Ratos Sprague-Dawley , Cloaca/embriologia , Cloaca/metabolismo
5.
Bioorg Chem ; 146: 107311, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38547720

RESUMO

In the course of our investigations of antifungal natural products, the structure-activity relationship and antifungal activities of oleanolic acid-type saponins (1-28) from Pulsatilla chinensis against human and plant pathogenic fungi were elucidated. The analysis of structure-activity relationship of oleanolic acid-type saponins showed that the free carboxyl at C-28 was essential for their antifungal activities; the free hydroxyl group at the C-23 site of oleanolic acid-type saponins played a crucial role in their antifungal activities; the oligosaccharide chain at C-3 oleanolic acid-type saponins showed significant effects on antifungal efficacy and a disaccharide or trisaccharide moiety at position C-3 displayed optimal antifungal activity. The typical saponin pulchinenoside B3 (16, PB3) displayed satisfactory antifungal activity against human and plant pathogenic fungi, especially, C. albicans with an MIC value of 12.5 µg/mL. Furthermore, PB3 could inhibit the biofilm formation of C. albicans through downregulating the expression of the integrated network of biofilm formation-associated transcription factors (Bcr1 Efg1, Ndt80, Brg1, Rob1 and Tec1) and adhesion-related target genes (HWP1, ALS1, and ALS3). Meanwhile, we found that PB3 could effectively destroy the mature biofilm of C. albicans by the oxidative damage and inducing mitochondria-mediated apoptosis in cells.


Assuntos
Ácido Oleanólico , Pulsatilla , Saponinas , Humanos , Antifúngicos/farmacologia , Biofilmes , Candida albicans , Saponinas/farmacologia , Relação Estrutura-Atividade , Animais
6.
J Appl Toxicol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981847

RESUMO

The overactivation of ß-adrenergic receptors (ß-ARs) can result in acute myocardial ischemic injury, culminating in myocardial necrosis. Berberine (BBR) has exhibited promising potential for prevention and treatment in various heart diseases. However, its specific role in mitigating myocardial injury induced by acute ß-AR overactivation remains unexplored. This study aimed to investigate the effects and underlying mechanisms of BBR pretreatment in a rat model of acute ß-AR overactivation induced by a single dose of the nonselective ß-adrenergic agonist isoprenaline (ISO). Rats were pretreated with saline or BBR (100 mg/kg/day) via gavage for 14 consecutive days, followed by a subcutaneous injection of ISO or saline on the 14th day. The findings indicated that BBR pretreatment significantly attenuated myocardial injury in ISO-stimulated rats, as evidenced by reduced pathological inflammatory infiltration, necrosis, and serum markers of myocardial damage. Additionally, BBR decreased oxidative stress and inflammation in the system and heart. Furthermore, BBR pretreatment enhanced myocardial ATP levels, improved mitochondrial dysfunction through increased Drp1 phosphorylation, and augmented myocardial autophagy. In a CoCl2-induced H9c2 cell hypoxic injury model, BBR pretreatment mitigated cellular injury, apoptosis, and oxidative stress while upregulating Drp1 and autophagy-associated proteins. Mechanistically, BBR pretreatment activated AKT, AMPK, and LKB1 both in vivo and in vitro, implicating the involvement of the AKT and LKB1/AMPK signaling pathways in its cardioprotective effects. Our study demonstrated the protective effects of BBR against myocardial injury induced by acute ß-AR overactivation in rats, highlighting the potential of BBR as a preventive agent for myocardial injury associated with ß-adrenergic overactivation.

7.
Chem Biodivers ; 21(8): e202401093, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38867371

RESUMO

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.


Assuntos
Apiaceae , Cumarínicos , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Cumarínicos/química , Cumarínicos/farmacologia , Cumarínicos/isolamento & purificação , Apiaceae/química , Animais , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Ciclo-Oxigenase 2/metabolismo , Camundongos , Células RAW 264.7 , Raízes de Plantas/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação
8.
Angew Chem Int Ed Engl ; 63(32): e202405905, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38771269

RESUMO

The replacement of a CC unit with an isoelectronic BN unit in aromatic systems can give rise to molecules and materials with fascinating properties. We report here the synthesis, characterization, and reactivity of a 1,4,2,3-diazadiborole species, 2, featuring an unprecedented 6π-aromatic BN-heterocyclic moiety that is isoelectronic to cyclopentadienide (Cp-). Bearing an unsymmetrical B=B entity, 2 exhibits reactivity toward oxidants, protic reagents, electrophiles, and unsaturated substrates. This reactivity facilitates the synthesis of a variety of novel mono- and bicyclic organoboron derivatives through mechanisms including ring retention, cleavage/recombination, annulation, and expansion. These findings reveal innovative synthetic routes to BN-embedded aromatic compounds via desymmetrization, affording unique building blocks for synthetic chemistry.

9.
Angew Chem Int Ed Engl ; : e202409286, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39018503

RESUMO

Rechargeable Mg batteries are a promising energy storage technology to overcome the limitations inherent to Li ion batteries. A critical challenge in advancing Mg batteries is the lack of suitable cathode materials. In this work, we report a cathode design that incorporates S functionality into two-dimensional metal-organic-frameworks (2D-MOFs). This new cathode material enables good Mg2+ storage capacity and outstanding cyclability. It was found that upon the initial Mg2+ insertion and disinsertion, there is an apparent structural transformation that crumbles the layered 2D framework, leading to amorphization. The resulting material serves as the active material to host Mg2+ through reduction and/or oxidation of S and, to a limited extent, O. The reversible nature of S and O redox chemistry was confirmed by spectroscopic characterizations and validated by density functional calculations. Importantly, during the Mg2+ insertion and disinsertion process, the 2D nature of the framework was maintained, which plays a key role in enabling the high reversibility of the MOF cathode.

11.
Food Res Int ; 191: 114645, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39059901

RESUMO

Mechanization has emerged as a focal point in the modernization of traditional enterprises, offering standardized production and labor reduction benefits. However, little is known about how mechanization affects the microbiota and metabolite profiles of Daqu. To address this gap, we conducted a comprehensive comparison between traditional and mechanical sauce-flavor Daqu using a multi-omics approach. Results showed that mechanical Daqu exhibited higher acidity, amino acid nitrogen and enzyme activity, alongside lower fat and moisture levels. Following mechanization, lactic acid bacteria (LAB), Staphylococcus, Aspergillus and Saccharomycopsis were enriched and identified as biomarkers, whereas Oceanobacillus, Monascus and Scopulariopsis were notably decreased. Furthermore, significant disparities in metabolic profiles were observed between the two types of Daqu based on GC-MS, GC-IMS, and LC-MS/MS analyses. The content of volatile compounds was significantly higher in mechanical Daqu (332.82 ± 22.69 mg/kg), while that of non-volatile compounds was higher in traditional Daqu (753.44 ± 41.82 mg/kg). Moreover, OPLS-DA models identified 44 volatile and 31 non-volatile compounds as differential metabolites. Multivariate statistical analysis indicated that bacteria and fungi primarily contributed to protease and saccharification activities, respectively. Additionally, the co-occurrence network revealed that Oceanobacillus and Scopulariopsis were closely associated with non-volatile compound formation, while LAB and Rhizopus significantly influenced volatile compound production. These findings elucidate the multi-dimensional relationship between mechanization and Daqu quality, offering insights to advance the modernization of traditional industries.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Manipulação de Alimentos/métodos , Metabolômica/métodos , Cromatografia Gasosa-Espectrometria de Massas , Aromatizantes/metabolismo , Microbiologia de Alimentos/métodos , Paladar , Microbiota , Lactobacillales/metabolismo , Lactobacillales/genética , Metaboloma
12.
Food Res Int ; 176: 113805, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163713

RESUMO

The enzyme activity of Daqu is an important prerequisite for defining it as a Baijiu starter. However, little is known about the functional species related to enzymes in different types of Daqu at the metagenomic level. Therefore, we analyzed the differences in enzymatic properties, microbial composition and metabolic function of three types of Daqu, namely high-, medium- and low-temperature Daqus (HTD, MTD and LTD), by combining chemical feature and multi-dimensional sequencing. The results showed that both liquefaction, saccharification, fermentation and esterification powers were remarkably weaker in HTD compared to MTD and LTD. Totally, 30 bacterial and 5 fungal phyla were identified and significant differences in community structures were also observed among samples, with Brevibacterium/Microascus, Pseudomonas, and Lactobacillus/Saccharomycopsis identified as biomarkers for HTD, MTD and LTD, respectively. Additionally, the importance of deterministic assembly in bacterial communities was proportional to the fermentation peak-temperature, while stochastic assembly dominated in fungal ones. Metagenomics analysis indicated eukaryota (>80 %, mainly Ascomycota) predominated in HTD and MTD while bacteria (54.3 %, mainly Actinobacteriota) were more abundant in LTD. However, the functional profiles and pathways of MTD and LTD were more similar, and the synthesis and metabolism of carbohydrates and amino acids were the crucial biological functions of all samples. Finally, the relationship between species and enzymes in different samples was constructed and the functional species in LTD and MTD were more diverse than HTD, which elucidated the functional species associated with enzyme activity in each type of Daqu. These results will greatly enrich our understanding of the core functional species in three typical Daqu, which provide available information for rational regulation of Daqu quality and the Baijiu fermentation.


Assuntos
Bebidas Alcoólicas , Bactérias , Fermentação , Bebidas Alcoólicas/microbiologia , Temperatura , Bactérias/genética , Bactérias/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala
13.
Front Pharmacol ; 15: 1394941, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903998

RESUMO

Context: It is very necessary to delay ovarian aging and prevent age-related health problems. The active ingredient in Honghua Xiaoyao tablet (HHXYT) has the effects of anti-oxidation, anti-inflammation, immune regulation and so on. Objective: To explore the effect and mechanism of Honghua Xiaoyao tablet on aging model mice. Materials and methods: The aging model was established by intraperitoneal injection of D-galactose in model mice. The mice in the HHXYT-L,M,H group were given 0.3 g/kg, 0.6 g/kg and 1.2 g/kg Honghua Xiaoyao tablet suspension respectively, and the HHXYT-M + E2 group was given 0.6 g/kg HHXYT +0.13 mg/kg estradiol valerate for 30 days. In this study, ELISA, HE, Western blot, IH and TUNEL were used. Results: HHXYT + E2 can improve the gonadal index, estrous cycle of aging mice. In HHXYT-M + E2 group, the level of FSH and LH decreased, while E2 and AMH increased significantly. The number of growing follicles in HHXYT-M + E2 group increased, which was better than that of HHXYT alone. Western blot results showed that HHXYT-M + E2 group decreased the expression of Bax, cleaved-Parp, cleaved-Casp-3 and CytC molecules and increased the expression of Bcl-2 in ovarian tissue. FSHR expression decreased in model group and increased in HHXYT group. TUNEL staining showed that the number of apoptotic cells in HHXYT group was reduced, and the HHXYT-M + E2 group was the most significantly. Discussion and conclusion: HHXYT can improve the level of sex hormones and increase the number of growing follicles in aging mice. HHXYT-M + E2 group has the best effect, and its mechanism may be related to reducing ovarian granulosa cell apoptosis.

14.
Nutrients ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732519

RESUMO

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVDs) that has become a global public health problem. Puerarin (PUE), the principal active compound of Pueraria lobata, has the effects of regulating glucose and lipid metabolism and protecting against cardiovascular damage. This study aimed to investigate whether dietary supplementation with PUE could ameliorate MetS and its associated cardiovascular damage. Rats were randomly divided into three groups: the normal diet group (NC), the high-fat/high-sucrose diet group (HFHS), and the HFHS plus PUE diet group (HFHS-PUE). The results showed that PUE-supplemented rats exhibited enhanced glucose tolerance, improved lipid parameters, and reduced blood pressure compared to those on the HFHS diet alone. Additionally, PUE reversed the HFHS-induced elevations in the atherogenic index (AI) and the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Ultrasonic evaluations indicated that PUE significantly ameliorated cardiac dysfunction and arterial stiffness. Histopathological assessments further confirmed that PUE significantly mitigated cardiac remodeling, arterial remodeling, and neuronal damage in the brain. Moreover, PUE lowered systemic inflammatory indices including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). In conclusion, dietary supplementation with PUE effectively moderated metabolic disorders, attenuated systemic inflammation, and minimized cardiovascular damage in rats with MetS induced by an HFHS diet. These results provide novel insights into the potential benefits of dietary PUE supplementation for the prevention and management of MetS and its related CVDs.


Assuntos
Doenças Cardiovasculares , Dieta Hiperlipídica , Isoflavonas , Síndrome Metabólica , Animais , Síndrome Metabólica/etiologia , Síndrome Metabólica/tratamento farmacológico , Isoflavonas/farmacologia , Dieta Hiperlipídica/efeitos adversos , Masculino , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Ratos , Suplementos Nutricionais , Ratos Sprague-Dawley , Pressão Sanguínea/efeitos dos fármacos , Glicemia/metabolismo , Sacarose Alimentar/efeitos adversos , Rigidez Vascular/efeitos dos fármacos , Modelos Animais de Doenças , Lipídeos/sangue , Pueraria/química
15.
Sci China Life Sci ; 67(8): 1739-1750, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38748355

RESUMO

The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.


Assuntos
COVID-19 , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Humanos , COVID-19/epidemiologia , COVID-19/microbiologia , COVID-19/virologia , Lactente , Pré-Escolar , Feminino , Masculino , RNA Ribossômico 16S/genética , Criança , Fezes/microbiologia , Fezes/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Pequim/epidemiologia , Pandemias , Carga Bacteriana , Estudos de Coortes , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação
16.
J Agric Food Chem ; 72(15): 8521-8535, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38565849

RESUMO

Thirty-five norsesquiterpenoids were isolated from the fermentation broth of Streptomyces microflavus from the forest soil of Ailaoshan in China. The structures of new compounds (1-5, 10-26) were elucidated by comprehensive spectroscopic analysis including data from experimental and calculated ECD spectra, as well as Mosher's reagent derivatives method. Norsesquiterpenoids showed different levels of antifungal activity with MIC80 values ranging from 25 to 200 µg/mL against Candida albicans, Candida parapsilosis, and Cryptococcus neoformans. The combining isolated norsesquiterpenoids with amphotericin B resulted in a synergistic interaction against test yeast-like fungi with a fractional inhibitory concentration index < 0.5. Compound 33 significantly inhibited biofilm formation and destroyed the preformed biofilm of fungi. Moreover, 33 downregulated the expression of adhesion-related genes HWP1, ALS1, ALS3, ECE1, EAP1, and BCR1 to inhibit the adhesion of C. albicans. Findings from the current study highlight the potential usage of norsesquiterpenoids from soil-derived Streptomyces for antifungal leads discovery.


Assuntos
Antifúngicos , Streptomyces , Antifúngicos/farmacologia , Anfotericina B/farmacologia , Candida albicans , Streptomyces/genética , Biofilmes , Testes de Sensibilidade Microbiana
17.
Front Immunol ; 15: 1356075, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529274

RESUMO

Background: During aging, chronic inflammation can promote tumor development and metastasis. Patients with chronic inflammatory bowel diseases (IBD) are at an increased risk of developing colorectal cancer (CRC). However, the molecular mechanism underlying is still unclear. Methods: We conducted a large-scale single-cell sequencing analysis comprising 432,314 single cells from 92 CRC and 24 IBD patients. The analysis focused on the heterogeneity and commonality of CRC and IBD with respect to immune cell landscape, cellular communication, aging and inflammatory response, and Meta programs. Results: The CRC and IBD had significantly different propensities in terms of cell proportions, differential genes and their functions, and cellular communication. The progression of CRC was mainly associated with epithelial cells, fibroblasts, and monocyte-macrophages, which displayed pronounced metabolic functions. In particular, monocyte-macrophages were enriched for the aging and inflammation-associated NF-κB pathway. And IBD was enriched in immune-related functions with B cells and T cells. Cellular communication analysis in CRC samples displayed an increase in MIF signaling from epithelial cells to T cells, and an increase in the efferent signal of senescence-associated SPP1 signaling from monocyte-macrophages. Notably, we also found some commonalities between CRC and IBD. The efferent and afferent signals showed that the pro-inflammatory cytokine played an important role. And the activity of aging and inflammatory response with AUCell analysis also showed a high degree of commonality. Furthermore, using the Meta programs (MPs) with the NMF algorithm, we found that the CRC non-malignant cells shared a substantial proportion of the MP genes with CRC malignant cells (68% overlap) and IBD epithelial cells (52% overlap), respectively. And it was extensively involved in functions of cell cycle and immune response, revealing its dual properties of inflammation and cancer. In addition, CRC malignant and non-malignant cells were enriched for the senescence-related cell cycle G2M phase transition and the p53 signaling pathway. Conclusion: Our study highlights the characteristics of aging, inflammation and tumor in CRC and IBD at the single-cell level, and the dual property of inflammation-cancer in CRC non-malignant cells may provide a more up-to-date understanding of disease transformation.


Assuntos
Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Transcriptoma , Inflamação/genética , Inflamação/complicações , Citocinas , Microambiente Tumoral/genética
18.
J Agric Food Chem ; 72(17): 10089-10096, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626386

RESUMO

Lactoferrin (LTF) has diverse biological activities and is widely used in functional foods and active additives. Nevertheless, evaluating the proteoform heterogeneity, conformational stability, and activity of LTF remains challenging during its production and storage processes. In this study, we describe the implementation of native mass spectrometry (nMS), glycoproteomics, and an antimicrobial activity assay to assess the quality of LTF. We systematically characterize the purity, glycosylation heterogeneity, conformation, and thermal stability of LTF samples from different sources and transient high-temperature treatments by using nMS and glycoproteomics. Meanwhile, the nMS peak intensity and antimicrobial activity of LTF samples after heat treatment decreased significantly, and the two values were positively correlated. The nMS results provide essential molecular insights into the conformational stability and glycosylation heterogeneity of different LTF samples. Our results underscore the great potential of nMS for LTF quality control and activity evaluation in industrial production.


Assuntos
Lactoferrina , Espectrometria de Massas , Lactoferrina/química , Lactoferrina/metabolismo , Glicosilação , Estabilidade Proteica , Animais , Conformação Proteica , Bovinos , Temperatura Alta
19.
Clin Genitourin Cancer ; 22(4): 102095, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38833825

RESUMO

INTRODUCTION BACKGROUND: Disulfidptosis is a prevalent apoptotic mechanism, intrinsically linked to cancer prognosis. However, the specific involvement of disulfidptosis-related long non-coding RNA (DRLncRNAs) in Kidney renal clear cell carcinoma (KIRC) remains incompletely understood. This study aims to elucidate the potential prognostic significance of disulfidptosis-related LncRNAs in KIRC. MATERIALS AND METHODS: Expression profiles and clinical data of KIRC patients were retrieved from the TCGA database to discern differentially expressed DRLncRNAs correlated with overall survival. Cox univariate analysis, Lasso Regression, and Cox multivariate analysis were used to construct a clinical prediction model. RESULTS: Six signatures, namely FAM83C.AS1, AC136475.2, AC121338.2, AC026401.3, AC254562.3, and AC000050.2, were established to evaluate overall survival (OS) in the context of Kidney renal clear cell carcinoma (KIRC) in this study. Survival analysis and ROC curves demonstrated the strong predictive performance of the associated signature. The nomogram exhibited accurate prognostic predictions for overall patient survival, offering substantial clinical utility. Gene set enrichment analysis revealed that risk signals were enriched in various immune-related pathways. Furthermore, the risk features exhibited significant correlations with immune cells, immune function, immune cell infiltration, and immune checkpoints. CONCLUSION: This study has unveiled, for the first time, six disulfdptosis-related LncRNA signatures, laying a solid foundation for enhanced and precise prognostic predictions in KIRC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Prognóstico , Masculino , Feminino , Biomarcadores Tumorais/genética , Nomogramas , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Apoptose , Análise de Sobrevida
20.
Pest Manag Sci ; 80(9): 4175-4185, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38587094

RESUMO

BACKGROUND: The fall armyworm (FAW, Spodoptera frugiperda (J.E. Smith)) is a polyphagous agricultural pest with rapidly evolving adaptations to host plants. We found the oral secretion (OS) of FAW from different plants influences plant defense response differentially, suggesting its role in adapting to host plants. However, the protein expression profile of FAW OS respond to different plants is largely unknown. RESULTS: Here, from the mass spectrometry assay, we identified a total of 256 proteins in the OS of FAW fed on cotton (Gossypium hirsutum L.), tobacco (Nicotiana benthamiana Domin), maize (Zea mays L.) and artificial diet. The FAW OS primarily comprise of 60 proteases, 32 esterases and 92 non-enzymatic proteins. It displays high plasticity across different diets. We found that more than half of the esterases are lipases which have been reported as insect elicitors to enhance plant defense response. The lipase accumulation in cotton-fed larvae was the highest, followed by maize-fed larvae. In the presence of lipase inhibitors, the enhanced induction on defense genes in wounded leaves by OS was attenuated. However, the putative effectors were most highly accumulated in the OS from FAW larvae fed on maize compared to those fed on other diets. We identified that one of them (VRLP4) reduces the OS-mediated induction on defense genes in wounded leaves. CONCLUSION: Together, our investigation presents the proteomic landscape of the OS of FAW influenced by different diets and reveals diet-mediated plasticity of OS is involved in FAW adaptation to host plants. © 2024 Society of Chemical Industry.


Assuntos
Adaptação Fisiológica , Larva , Spodoptera , Zea mays , Animais , Spodoptera/fisiologia , Spodoptera/genética , Larva/fisiologia , Larva/metabolismo , Larva/crescimento & desenvolvimento , Zea mays/genética , Zea mays/metabolismo , Nicotiana/metabolismo , Nicotiana/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteoma , Gossypium/genética , Gossypium/metabolismo , Proteômica , Saliva/química , Saliva/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA