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1.
Hepatology ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407233

RESUMO

BACKGROUND AND AIMS: Liver ischemia-reperfusion injury (IRI) is a common complication of liver transplantation and hepatectomy and causes acute liver dysfunction and even organ failure. Myeloid-derived suppressor cells (MDSCs) accumulate and play immunosuppressive function in cancers and inflammation. However, the role of MDSCs in liver IRI has not been defined. APPROACH AND RESULTS: We enrolled recipients receiving OLT and obtained the pre-OLT/post-OLT blood and liver samples. The proportions of MDSCs were significantly elevated after OLT and negatively associated with liver damage. In single-cell RNA-sequencing analysis of liver samples during OLT, 2 cell clusters with MDSC-like phenotypes were identified and showed maturation and infiltration in post-OLT livers. In the mouse model, liver IRI mobilized MDSCs and promoted their infiltration in the damaged liver, and intrahepatic MDSCs were possessed with enhanced immunosuppressive function by upregulation of STAT3 signaling. Under treatment with αGr-1 antibody or adoptive transfer MDSCs to change the proportion of MDSCs in vivo, we found that intrahepatic MDSCs alleviated liver IRI-induced inflammation and damage by inhibiting M1 macrophage polarization. Mechanistically, bulk RNA-sequencing analysis and in vivo experiments verified that C-X-C motif chemokine ligand 17 (CXCL17) was upregulated by YAP/TEAD1 signaling and subsequently recruited MDSCs through binding with GPR35 during liver IRI. Moreover, hepatic endothelial cells were the major cells responsible for CXCL17 expression in injured livers, among which hypoxia-reoxygenation stimulation activated the YAP/TEAD1 complex to promote CXCL17 transcription. CONCLUSIONS: Endothelial YAP/TEAD1-CXCL17 signaling recruited MDSCs to attenuate liver IRI, providing evidence of therapeutic potential for managing IRI in liver surgery.

2.
Clin Gastroenterol Hepatol ; 21(10): 2560-2569.e15, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36202348

RESUMO

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) was recently proposed as an alternative name change for better encapsulation of disease. However, there exists a spectrum of MAFLD where both metabolically healthy (MH) and metabolically unhealthy (MU) individuals are included. In view of limited evidence, we sought to examine the prevalence, clinical characteristics, and differences in outcomes of MH-MAFLD at the population level. METHODS: Data were used from the United States National Health and Nutrition Examination Survey 1999 to 2018. Multivariate logistic regression analysis was used to obtain odds ratios for the estimation of events. Survival analysis was conducted with Cox regression and the Fine-Gray subdistribution model. RESULTS: There were 32,683 overweight and obese individuals included in the analysis. In MAFLD patients, the prevalence of MH-MAFLD was 6.92% (95% confidence interval [CI], 6.58%-7.27%), and 93.08% (95% CI, 92.73%-93.42%) were considered as MU-MAFLD. Multivariate analysis found a significantly higher risk of MACE (odds ratio, 1.38; 95% CI, 1.28-1.49; P < .01), all-cause (hazard ratio, 1.24; 95% CI, 1.17-1.32; P < .01), cardiovascular disease (SHR, 1.20; 95% CI, 1.02-1.42; P = .03), and cancer mortality (SHR, 1.24; 95% CI, 1.07-1.44; P < .01) in MU-MAFLD relative to non-MAFLD. However, MH-MAFLD individuals were not associated with a statistically significant increased risk of these adverse outcomes compared with non-MAFLD. MU-MAFLD diabetics were also at a higher risk of adverse events compared with non-diabetics. CONCLUSIONS: This study reports on the heterogeneity and spectrum of metabolic dysfunction that exists in overweight and obese MAFLD. Although MAFLD may potentially be advantageous in improving awareness and patient outcomes, there remains substantial heterogeneity within patients included in MAFLD on the basis of the underlying metabolic burden.


Assuntos
Doenças Cardiovasculares , Hepatopatia Gordurosa não Alcoólica , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Inquéritos Nutricionais , Obesidade/complicações , Obesidade/epidemiologia , Nível de Saúde
3.
Molecules ; 26(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34833903

RESUMO

Multi-drug resistance (MDR) bacterial pathogens pose a threat to global health and warrant the discovery of new therapeutic molecules, particularly those that can neutralize their virulence and stop the evolution of new resistant mechanisms. The superbug nosocomial pathogen, Pseudomonas aeruginosa, uses a multiple virulence factor regulator (MvfR) to regulate the expression of multiple virulence proteins during acute and persistent infections. The present study targeted MvfR with the intention of designing novel anti-virulent compounds, which will function in two ways: first, they will block the virulence and pathogenesis P. aeruginosa by disrupting the quorum-sensing network of the bacteria, and second, they will stop the evolution of new resistant mechanisms. A structure-based virtual screening (SBVS) method was used to screen druglike compounds from the Asinex antibacterial library (~5968 molecules) and the comprehensive marine natural products database (CMNPD) (~32 thousand compounds), against the ligand-binding domain (LBD) of MvfR, to identify molecules that show high binding potential for the relevant pocket. In this way, two compounds were identified: Top-1 (4-((carbamoyloxy)methyl)-10,10-dihydroxy-2,6-diiminiodecahydropyrrolo[1,2-c]purin-9-yl sulfate) and Top-2 (10,10-dihydroxy-2,6-diiminio-4-(((sulfonatocarbamoyl)oxy)methyl)decahydropyrrolo[1,2-c]purin-9-yl sulfate), in contrast to the co-crystallized M64 control. Both of the screened leads were found to show deep pocket binding and interactions with several key residues through a network of hydrophobic and hydrophilic interactions. The docking results were validated by a long run of 200 ns of molecular dynamics simulation and MM-PB/GBSA binding free energies. All of these analyses confirmed the presence of strong complex formation and rigorous intermolecular interactions. An additional analysis of normal mode entropy and a WaterSwap assay were also performed to complement the aforementioned studies. Lastly, the compounds were found to show an acceptable range of pharmacokinetic properties, making both compounds potential candidates for further experimental studies to decipher their real biological potency.


Assuntos
Antibacterianos/farmacologia , Pseudomonas aeruginosa/patogenicidade , Fatores de Virulência/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/farmacocinética , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/fisiologia , Sítios de Ligação , Bases de Dados de Produtos Farmacêuticos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana Múltipla , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Bibliotecas de Moléculas Pequenas , Interface Usuário-Computador , Fatores de Virulência/química , Fatores de Virulência/fisiologia
4.
Environ Res ; 188: 109829, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32798948

RESUMO

Intensive studies have been performed on the improvement of bioethanol production by transformation of lignocellulose biomass. In this study, the digestibility of corn stover was dramatically improved by using laccase immobilized on Cu2+ modified recyclable magnetite nanoparticles, Fe3O4-NH2. After digestion, the laccase was efficiently separated from slurry. The degradation rate of lignin reached 40.76%, and the subsequent cellulose conversion rate 38.37% for 72 h at 35 °C with cellulase at 50 U g-1 of corn stover. Compared to those of free and inactivated mode, the immobilized laccase pre-treatment increased subsequent cellulose conversion rates by 23.98% and 23.34%, respectively. Moreover, the reusability of immobilized laccase activity remained 50% after 6 cycles. The storage and thermal stability of the fixed laccase enhanced by 70% and 24.1% compared to those of free laccase at 65 °C, pH 4.5, respectively. At pH 10.5, it exhibited 16.3% more activities than its free mode at 35 °C. Our study provides a new avenue for improving the production of bioethanol with immobilized laccase for delignification using corn stover as the starting material.


Assuntos
Celulase , Nanopartículas de Magnetita , Hidrólise , Lacase , Zea mays
5.
J Autoimmun ; 100: 84-94, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30872080

RESUMO

TREX1 encodes a major cellular DNA exonuclease. Mutations of this gene in human cause cellular accumulation of DNA that triggers autoimmune diseases including Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). We created a lupus mouse model by engineering a D18 N mutation in the Trex1 gene which inactivates the enzyme and has been found in human patients with lupus-like disorders. The Trex1D18N/D18N mice exhibited systemic inflammation that consistently recapitulates many characteristics of human AGS and SLE. Importantly, ablation of cGas gene in the Trex1D18N/D18N mice rescued the lethality and all detectable pathological phenotypes, including multi-organ inflammation, interferon stimulated gene induction, autoantibody production and aberrant T-cell activation. These results indicate that cGAS is a key mediator in the autoimmune disease associated with defective TREX1 function, providing additional insights into disease pathogenesis and guidance to the development of therapeutics for human systemic autoimmune disorders.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Exodesoxirribonucleases , Lúpus Eritematoso Sistêmico , Ativação Linfocitária , Mutação de Sentido Incorreto , Malformações do Sistema Nervoso , Nucleotidiltransferases , Fosfoproteínas , Linfócitos T/imunologia , Substituição de Aminoácidos , Animais , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/patologia , Modelos Animais de Doenças , Ativação Enzimática/genética , Ativação Enzimática/imunologia , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/imunologia , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Mutantes , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/imunologia , Malformações do Sistema Nervoso/patologia , Nucleotidiltransferases/genética , Nucleotidiltransferases/imunologia , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Linfócitos T/patologia
6.
J Basic Microbiol ; 59(7): 744-753, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087563

RESUMO

The recalcitrance of lignocellulosic biomass is a major factor limiting its conversion into biofuels. Therefore, in this study, we pretreated corn stalk with 2% Na2 CO3 and 2% H2 O2 for time 70 min at 130°C using a corn stalk to liquid ratio of 1:10. The fermentation broth from multicopy Saccharomyces cerevisiae strains engineered for lignocellulase synthesis was used to enzymatically hydrolyze the pretreated corn stalk. The highest monosaccharide yield (102 mmol/L) was obtained using 15 IU endocellulase, 10 IU exocellulase, and 15 IU ß-glucosidase per gram of cellulose and 20 IU xylanase per gram of hemicellulose. Subsequently, the high-efficiency ethanol-producing S. cerevisiae strain WXY12, which can produce ethanol from glucose and xylose simultaneously, was added to the fermentation system. The entire process involved ethanol production through simultaneous saccharification and fermentation (SSF). Optimization of the fermentation conditions (yeast powder as a nitrogen source, temperature of 30°C, MgSO4 as a metal ion inducer, rotation speed of 180 rpm, solid-liquid ratio of 1:8, and inoculation amount of 2%) resulted in an ethanol output of 46.87 g/L and a theoretical conversion rate of 27.4%. The results of this study improved corn stalk utilization, reduced hydrolysis costs, and generated high ethanol yields.


Assuntos
Biocombustíveis , Etanol/metabolismo , Fermentação , Saccharomyces cerevisiae/metabolismo , Zea mays/química , Zea mays/metabolismo , Bioengenharia , Biomassa , Hidrólise , Lignina/química , Lignina/metabolismo , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
7.
Molecules ; 24(20)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658589

RESUMO

Acting as a "green" manufacturing route, the enzyme toolbox made up of galactose oxidase, catalase, and horseradish peroxidase can achieve a satisfactory yield of 2,5-diformylfuran derived from 30 mM hydroxymethylfurfural. However, as the concentration of hydroxymethylfurfural increases, the substrate causes oxidative damage to the activity of the tri-enzyme system, and the accumulated hydrogen peroxide produced by galactose oxidase causes tri-enzyme inactivation. The cost of tri-enzymes is also very high. These problems prevent the utilization of this enzyme toolbox in practice. To address this, galactose oxidase, catalase, and horseradish peroxidase were co-immobilized into Cu3(PO4)2 nanoflowers in this study. The resulting co-immobilized tri-enzymes possessed better tolerance towards the oxidative damage caused by hydroxymethylfurfural at high concentrations, as compared to free tri-enzymes. Moreover, the 2,5-diformylfuran yield of co-immobilized tri-enzymes (95.7 ± 2.7%) was 1.06 times higher than that of separately immobilized enzymes (90.4 ± 1.9%). This result could be attributed to the boosted protective effect provided by catalase to the activity of galactose oxidase, owing to the physical proximity between them on the same support. After 30 recycles, co-immobilized tri-enzymes still achieves 86% of the initial yield. Moreover, co-immobilized tri-enzymes show enhanced thermal stability compared with free tri-enzymes. This work paves the way for the production of 2,5-diformylfuran from hydroxymethylfurfural via co-immobilized tri-enzymes.


Assuntos
Catalase/química , Enzimas Imobilizadas/química , Furaldeído/análogos & derivados , Furanos/síntese química , Glucose Oxidase/química , Furaldeído/química , Peroxidase do Rábano Silvestre/química , Oxirredução
8.
Acta Obstet Gynecol Scand ; 95(2): 157-65, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26439908

RESUMO

INTRODUCTION: The aim of this study was to summarize evidence on the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and odds of preterm delivery and placental abruption. MATERIAL AND METHODS: PubMed, EMBASE, CBM (Chinese Biomedical Database) and CNKI (Chinese National Knowledge Infrastructure) were searched to identify eligible studies published in English or Chinese before 12 August 2014. The pooled odds ratios (ORs) with 95% confidence intervals were estimated for the association of MTHFR C677T polymorphism with preterm delivery and placental abruption using random effects models. RESULTS: A total of 22 studies that met inclusion and exclusion criteria were included in this meta-analysis. Regardless of the genetic model tested we found no statistically significant association of MTHFR C677T polymorphism with preterm delivery or placental abruption. Funnel plots inspections, Begg's test and Egger's test did not show evidence of publication bias. CONCLUSIONS: This meta-analysis demonstrated that overall there was no association of MTHFR C677T polymorphism with preterm delivery or placental abruption.


Assuntos
Descolamento Prematuro da Placenta/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Nascimento Prematuro/genética , Feminino , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez
9.
ACS Omega ; 9(19): 21144-21151, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38764635

RESUMO

Hepatic carcinoma is one of the leading causes of morbidity and mortality among all cancers, but no effective treatment measures have been developed. Herein, polystyrene polysaccharide (PSP) extracted from Polygonatum was used to synthesize gold nanoparticles (PSP-AuNPs) by heating and reduction methods, and the characteristics of the PSP-AuNPs were detected after successful synthesis. In vitro, the immunoregulatory effects of PSP-AuNPs were studied by testing the concentrations of NO, TNF-α, and IL-12p70 in the culture media of PSP-AuNPs-treated RAW264.7 macrophages, and the effect of biocompatibility on the viability of RAW264.7 macrophages and L02 cells was studied via a CCK-8 assay. In vivo, tumor-bearing mice were established and treated with PSP-AuNPs, and the anticancer effects were studied by detecting trends in tumor volume, tumor inhibition rate, and tumor cell proliferation index. Immunoregulation was assessed by evaluating the serum levels of TNF-α and IL-10, the CD4+/CD8+ lymphocyte ratio in peripheral blood and the spleen and thymus indices; toxicity was investigated by measuring body weight, liver and renal function indices. The results showed that PSP-AuNPs could regulate immune function both in vitro and in vivo with almost no toxicity. PSP-AuNPs exhibited excellent anticancer effects on hepatic carcinoma in vivo. The anticancer effect could be strengthened, and the toxicity could be reduced by the combined use of PSP-AuNPs and ADM. In conclusion, PSP-AuNPs could be effective as a therapy and adjuvant therapy for treating hepatic carcinoma, providing potential treatment strategies for this disease.

10.
Int J Biol Macromol ; : 133667, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969038

RESUMO

Targeting macrophages to regulate the tumor microenvironment is a promising strategy for treating cancer. This study developed a stable nano drug (PAP-SeNPs) using Se nanoparticles (SeNPs) and the Pholiota adiposa polysaccharide component (PAP-1a) and reported their physical stability, M2-like macrophages targeting efficacy and anti-hepatoma immunotherapy potential, as well as their molecular mechanisms. Furthermore, the zero-valent and well-dispersed spherical PAP-SeNPs were also successfully synthesized with an average size of 55.84 nm and a negative ζ-potential of -51.45 mV. Moreover, it was observed that the prepared PAP-SeNPs were stable for 28 days at 4 °C. Intravital imaging highlighted that PAP-SeNPs had the dual effect of targeting desirable immune organs and tumors. In vitro analyses showed that the PAP-SeNPs polarized M2-like macrophages towards the M1 phenotype to induce hepatoma cell death, triggered by the time-dependent lysosomal endocytosis in macrophages. Mechanistically, PAP-SeNPs significantly activated the Tlr4/Myd88/NF-κB axis to transform tumor-promoting macrophages into tumor-inhibiting macrophages and successfully initiated antitumor immunotherapy. Furthermore, PAP-SeNPs also enhanced CD3+CD4+ T cells and CD3+CD8+ T cells, thereby further stimulating anti-hepatoma immune responses. These results suggest that the developed PAP-SeNPs is a promising immunostimulant that can assist hepatoma therapy.

11.
Sci Rep ; 14(1): 10848, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740945

RESUMO

Bacterial cellulose (BC) is a natural polymer renowned for its unique physicochemical and mechanical attributes, including notable water-holding capacity, crystallinity, and a pristine fiber network structure. While BC has broad applications spanning agriculture, industry, and medicine, its industrial utilization is hindered by production costs and yield limitations. In this study, Rhizobium sp. was isolated from bean roots and systematically assessed for BC synthesis under optimal conditions, with a comparative analysis against BC produced by Komagataeibacter hansenii. The study revealed that Rhizobium sp. exhibited optimal BC synthesis when supplied with a 1.5% glucose carbon source and a 0.15% yeast extract nitrogen source. Under static conditions at 30 °C and pH 6.5, the most favorable conditions for growth and BC production (2.5 g/L) were identified. Modifications were introduced using nisin to enhance BC properties, and the resulting BC-nisin composites were comprehensively characterized through various techniques, including FE-SEM, FTIR, porosity, swelling, filtration, and antibacterial activity assessments. The results demonstrated that BC produced by Rhizobium sp. displayed properties comparable to K. hansenii-produced BC. Furthermore, the BC-nisin composites exhibited remarkable inhibitory activity against Escherichia coli and Pseudomonas aeruginosa. This study contributes valuable insights into BC's production, modification, and characterization utilizing Rhizobium sp., highlighting the exceptional properties that render it efficacious across diverse applications.


Assuntos
Celulose , Raízes de Plantas , Rhizobium , Celulose/biossíntese , Celulose/metabolismo , Raízes de Plantas/microbiologia , Rhizobium/metabolismo , Acetobacteraceae/metabolismo , Antibacterianos/farmacologia , Antibacterianos/biossíntese
12.
Adv Mater ; 36(19): e2310443, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372054

RESUMO

Liver fibrosis represents a reversible stage of various chronic liver diseases that progresses to cirrhosis. This condition is characterized by an imbalance between tissue damage and repair, and the production of fibers in the liver exceeds their degradation. Oxidative stress (OS) resulting from tissue injury and endoplasmic reticulum stress (ERS) triggered by the overproduction of proteins are pivotal factors in liver fibrosis. Melatonin demonstrates the capability to neutralize free radicals, shielding cells from oxidative harm. It is also a specific inhibitor of the ERS receptor transcription activating factor 6 (ATF6), indicating its great potential in ameliorating liver fibrosis. However, its limited water solubility and oral bioavailability of under 15% present hurdles in achieving therapeutic blood concentrations for treating liver fibrosis. The PLGA@Melatonin is constructed by loading melatonin with poly (lactic-co-glycolic acid) (PLGA). Platelet membranes (PM) and activated hepatic stellate cell membranes (HSCM) with high expression of the platelet-derived growth factor receptor (PDGFR) are extracted to successfully construct PM@PLGA@Melatonin and HSCM@PLGA@Melatonin, which are subsequently utilized to treat mice with liver fibrosis. The results illustrated the remarkable therapeutic effects of the two nanoparticles on liver fibrosis, along with their excellent targeting and biosafety properties.


Assuntos
Membrana Celular , Estresse do Retículo Endoplasmático , Cirrose Hepática , Melatonina , Nanopartículas , Estresse Oxidativo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Estresse Oxidativo/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Melatonina/farmacologia , Melatonina/química , Camundongos , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Humanos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos
13.
Int J Biol Macromol ; 266(Pt 2): 131366, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580020

RESUMO

A functional starch (TPS-E) was designed and constructed by incorporating epoxy soybean oil (ESO) and an antibacterial agent polyhexamethylene guanidine hydrochloride (PHMG), then the film was prepared by reaction extrusion and blow molding using TPS-E and poly(butylene adipate-co-terephthalate) (PBAT). The micro-crosslinking structure, forming through ring-opening reaction between the epoxy active site of TPS-E and the end group of PBAT, improved the compatibility of starch/PBAT blend and reduce the dispersed starch phase size, leading to significantly increase the tensile strength. Compared to starch/PBAT films, the tensile strength of TPS-E/PBAT in the longitudinal direction increase by 112% with the same starch content of 30%. Furthermore, these TPS-E/PBAT films demonstrated long-lasting antibacterial performance with a 98% inhibition ratio even after 10 cycles, without any observed leaching of the antibacterial agent, highlighting the high coupling efficiency of PHMG. TPS-E with the degradable ESO also promotes the degradation of PBAT. Thus, an important method of synergistic improving the mechanical, degradable and antibacterial properties of blown films through the design of reactive micro-crosslinked starch structures was established.


Assuntos
Antibacterianos , Amido , Resistência à Tração , Amido/química , Antibacterianos/química , Antibacterianos/farmacologia , Poliésteres/química , Escherichia coli/efeitos dos fármacos , Fenômenos Mecânicos , Reagentes de Ligações Cruzadas/química , Staphylococcus aureus/efeitos dos fármacos
14.
Microorganisms ; 12(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38930441

RESUMO

The lack of efficient ways to dispose of lignocellulosic agricultural residues is a serious environmental issue. Low temperatures greatly impact the ability of organisms to degrade these wastes and convert them into nutrients. Here, we report the isolation and genomic characterization of a microbial consortium capable of degrading corn straw at low temperatures. The microorganisms isolated showed fast cellulose-degrading capabilities, as confirmed by scanning electron microscopy and the weight loss in corn straw. Bacteria in the consortium behaved as three diverse and functionally distinct populations, while fungi behaved as a single population in both diversity and functions overtime. The bacterial genus Pseudomonas and the fungal genus Thermoascus had prominent roles in the microbial consortium, showing significant lignocellulose waste-degrading functions. Bacteria and fungi present in the consortium contained high relative abundance of genes for membrane components, with amino acid breakdown and carbohydrate degradation being the most important metabolic pathways for bacteria, while fungi contained more genes involved in energy use, carbohydrate degradation, lipid and fatty acid decomposition, and biosynthesis.

15.
J Extracell Vesicles ; 13(6): e12466, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38887165

RESUMO

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.


Assuntos
Vesículas Extracelulares , Fígado , Humanos , Vesículas Extracelulares/metabolismo , Fígado/metabolismo , Microbioma Gastrointestinal , Animais , Trato Gastrointestinal/metabolismo , Alimentos
16.
J Cancer Res Clin Oncol ; 149(12): 10813-10829, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37316691

RESUMO

OBJECTIVES: There is increasing evidence for a close correlation between risk stratification, prognosis and the immune environment in colon adenocarcinoma (COAD). However, the efficacy of immunotherapy is different among different patients with COAD. Therefore, the current work tends to use immune-related gene to develop a gene-pair model to evaluate the COAD prognosis, and to develop a new method for risk stratification of COAD, which is conducive to better predict the immunotherapy effect of patients. METHODS: Specifically, from the TCGA and GEO (GSE14333 and GSE39582) databases, we first collected gene expression profiles, associated survival follow-up information of COAD patients. Through systematic bioinformatics analysis, we established a prognosis-related model of colon cancer with three pairs of "immune gene pairs", with uni- and multivariate and lasso cox regression analyses verifying the model stability. Most immune cells showed markedly different levels of infiltration between the two risk subgroups calculated by the model. More, single-cell RNA-seq analyses were also performed to validate the selected genes in the immune gene-pair model. RESULTS: A prognosis-related model of colon cancer with three pairs of "immune gene pairs" were built and validated by several datasets. The analysis of immune landscape of COAD revealed that low-risk subgroup obtained by the prognosis-related model for COAD can be further divided into three subclusters with different prognosis. Then, we applied the Tumor online Prognostic analyses Platform (ToPP) to construct a prognostic model using these five genes. Results show that APOD, ISG20 and STC2 are risk factors, while CXCL9 and IL7R are protection factors. We also found that only the five-gene model could also predict the prognosis of COAD patients, indicating the robustness of the gene-pair model. Among the five genes, including CXCL9, APOD, STC2, ISG20, and IL7R, in the gene-pair model, single-cell RNA sequencing reveals the high expression of CXCL9 and IL7R in inflammatory macrophages. Using cell-cell interaction and trajectory analysis, data indicate that CXCL9+/IL7R+ pro-inflammatory macrophages were capable of secreting and activating more anti-tumor pathways than CXCL9-/IL7R- pro-inflammatory macrophages. CONCLUSIONS: In short, we have successfully developed an "immune gene pair" related model that can judge the prognostic status of patients with COAD and may contribute to risk stratification and evaluate potential beneficiaries of immunotherapy, providing new ideas for the anti-COAD management and therapy.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/genética , Adenocarcinoma/genética , Transporte Biológico , Comunicação Celular , Biologia Computacional , Prognóstico
17.
Front Psychol ; 14: 1265536, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034314

RESUMO

Teaching is a demanding profession and maintaining teacher wellbeing is significant in ensuring educational quality. However, teacher wellbeing is easily affected by educational reforms, and systematic research on this topic is still relatively rare. In China, with the enactment of the Double Reduction Policy in 2021, the job characteristics of primary and secondary school teachers have undergone various changes. Thus, the current study examined the new job characteristics that China's Double Reduction Policy imposed on the wellbeing of school teachers and their relationships with teachers' inner world (i.e., emotional regulation and mindset). A cross-sectional study was carried out from June to October 2022 across China, employing self-reporting questionnaires for data collection and analysis. With a random sample of 902 teachers, we investigated the associations between teacher wellbeing, job characteristics, emotional regulation strategies, and mindset. The results indicated that teachers showed a lower level of wellbeing after the educational reform. Higher job resources contributed positively to predicting teacher wellbeing, while higher job demands contributed negatively. Genuinely expressing had positive impacts on teacher wellbeing while surface acting had negative impacts and deep acting none. Mindset was found to affect emotional regulation strategies and teacher wellbeing simultaneously. These findings shed light on how teachers can appropriately regulate emotions and maintain wellbeing in the wake of educational reforms.

18.
Sheng Wu Gong Cheng Xue Bao ; 39(3): 1083-1095, 2023 Mar 25.
Artigo em Zh | MEDLINE | ID: mdl-36994573

RESUMO

Biorefinery of chemicals from straw is an effective approach to alleviate the environmental pollution caused by straw burning. In this paper, we prepared gellan gum immobilized Lactobacillus bulgaricus T15 gel beads (LA-GAGR-T15 gel beads), characterized their properties, and established a continuous cell recycle fermentation process for D-lactate (D-LA) production using the LA-GAGR-T15 gel beads. The fracture stress of LA-GAGR-T15 gel beads was (91.68±0.11) kPa, which was 125.12% higher than that of the calcium alginate immobilized T15 gel beads (calcium alginate-T15 gel beads). This indicated that the strength of LA-GAGR-T15 gel beads was stronger, and the strain was less likely to leak out. The average D-LA production was (72.90±2.79) g/L after fermentation for ten recycles (720 h) using LA-GAGR-T15 gel beads as the starting strain and glucose as the substrate, which was 33.85% higher than that of calcium alginate-T15 gel beads and 37.70% higher than that of free T15. Subsequently, glucose was replaced by enzymatically hydrolyzed corn straw and fermented for ten recycles (240 h) using LA-GAGR-T15 gel beads. The yield of D-LA reached (1.74±0.79) g/(L·h), which was much higher than that of using free bacteria. The wear rate of gel beads was less than 5% after ten recycles, which indicated that LA-GAGR is a good carrier for cell immobilization and can be widely used in industrial fermentation. This study provides basic data for the industrial production of D-LA using cell-recycled fermentation, and provides a new way for the biorefinery of D-LA from corn straw.


Assuntos
Lactobacillus delbrueckii , Fermentação , Zea mays , Ácido Láctico , Alginatos/química , Glucose
19.
Materials (Basel) ; 16(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687639

RESUMO

To improve heat dissipation capability and enhance mechanical properties, a series of silica aerogel (SA) and modified glass fiber (GF)-filled SBR composites were prepared. It was found that the addition of SA successfully reduced the thermal conductivity of SBR by 35%, owing to the heat shield of the nanoscale porous structure of SA. Moreover, the addition of modified glass fiber (MGF) yielded a significant increase in the tensile and tear strength of SBR/SA composite rubber of 37% and 15%, respectively. This enhancement was more pronounced than the improvement observed with unmodified GF, and was attributed to the improved dispersion of fillers and crosslinking density of the SBR matrix. Rheological analysis revealed that the addition of SA and MGF weakened the ω dependence. This was due to the partial relaxation of immobilized rubber chains and limited relaxation of rubber chains adsorbed on the MGF. Furthermore, the strain amplification effect of MGF was stronger than that of GF, leading to a more pronounced reinforcing effect.

20.
Heliyon ; 9(2): e13246, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36755604

RESUMO

In this paper, the relationship between black liquor and microbial growth, enzymatic secretion and humus formation in composting was studied. The results showed that black liquor inoculation is an effective way to promote fermentation process. After black liquor inoculation, the abundance of Corynebacterium, Aequorivita, and Pedobacter, which have the catalase and oxidase activity, has been significantly increased. The enzymatic activity of alkaline phosphatase, catalase, peroxidase and invertase was 40 mg/(g·24h), 6.5 mg/(g·20 min), 13 100 mg/(g·24h), and 6100 mg/(g·24h) respectively at day 18. Humic acid and fulvic acid concentration was 12 g/kg and 11 g/kg which is higher than that of the treatments of no black liquor inoculation. The results suggested that black liquor inoculation was beneficial to indigenous microorganisms reproduce efficiently, then the secretion of enzymes related to cellulose, hemicellulose, and lipid hydrolysis, and the formation of humic substances.

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