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1.
Cell Death Discov ; 10(1): 272, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849356

RESUMO

Immune-related GTPase M (IRGM) induces autophagy and suppresses inflammation, but its putative role and signaling mechanism remain undefined in the pathogenesis of liver failure. This study aimed to address how IRGM attenuates inflammatory injury by regulating autophagy in liver failure. In this study, a total of 10 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and 10 healthy controls were prospectively enrolled. Intrahepatic expression of IRGM/Irgm1, NLRP3 inflammasome (NLRP3, ASC, and caspase-1), autophagy-related proteins (LC3II, P62), and inflammatory cytokines (IL-1ß, TNF-α) were measured. Autophagy was activated by rapamycin (4 mg/kg) in an acute liver failure (ALF) mouse model, which was used to further study the expression of Irgm1, NLRP3 inflammasome, autophagy-related proteins, and inflammatory cytokines using both qRT-PCR and Western blot analyses. Irgm1 expression was knocked down using Irgm1 short hairpin RNA (shRNA) in lipopolysaccharide (LPS)-induced AML12 cells to investigate the effects of Irgm1 deletion on autophagy and inflammation. We found that the expression of IRGM and autophagy-related proteins was significantly downregulated while the NLRP3 inflammasome was significantly upregulated in the livers of HBV-ACLF patients and the ALF mouse model (all P < 0.05). Rapamycin-induced autophagy ameliorated intrahepatic NLRP3 inflammasome activation and decreased inflammation and necrosis in the ALF mice. Irgm1 knockdown decreased autophagy and significantly upregulated NLRP3 inflammasome activation in AML12 cells (all P < 0.05). Rapamycin-induced autophagy also protected against hepatocyte injury following LPS stimulation in vitro by inhibiting NLRP3 inflammasome activation. Thus, IRGM/Irgm1 alleviates inflammation-mediated hepatocyte injury by regulating autophagy. This study provides new insight into potential molecular targets to treat liver failure.

2.
Nat Commun ; 15(1): 4058, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744836

RESUMO

Research on the development of cognitive selectivity predominantly focuses on attentional selection. The present study explores another facet of cognitive selectivity-memory selection-by examining the ability to filter attended yet outdated information in young children and adults. Across five experiments involving 130 children and 130 adults, participants are instructed to use specific information to complete a task, and then unexpectedly asked to report this information in a surprise test. The results consistently demonstrate a developmental reversal-like phenomenon, with children outperforming adults in reporting this kind of attended yet outdated information. Furthermore, we provide evidence against the idea that the results are due to different processing strategies or attentional deployments between adults and children. These results suggest that the ability of memory selection is not fully developed in young children, resulting in their inefficient filtering of attended yet outdated information that is not required for memory retention.


Assuntos
Atenção , Memória , Humanos , Feminino , Masculino , Adulto , Atenção/fisiologia , Criança , Memória/fisiologia , Adulto Jovem , Cognição/fisiologia , Pré-Escolar
3.
J Hazard Mater ; 472: 134593, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38749249

RESUMO

Due to the lack of research on the co-effects of microplastics and trace metals in the environment on nitrogen cycling-related functional microorganisms, the occurrence of microplastics and one of their plasticisers, phthalate esters, as well as trace metals, were determined in soils and river sediments in the Qinghai-Tibet Plateau. Relationship between microplastics and phthalate esters in the area was determined; the co-effects of these potentially toxic materials, and key factors and pathways affecting nitrogen functions were further explored. Significant correlations between fibre- and film-shaped microplastics and phthalate esters were detected in the soils from the plateau. Copper, lead, cadmium and di-n-octyl phthalate detected significantly affected nitrogen cycling-related functional microorganisms. The co-existence of di-n-octyl phthalate and copper in soils synergistically stimulated the expression of denitrification microorganisms nirS gene and "nitrate_reduction". Additionally, di-n-octyl phthalate and dimethyl phthalate more significantly affected the variation of nitrogen cycling-related functional genes than the number of microplastics. In a dimethyl phthalate- and cadmium-polluted area, nitrogen cycling-related functional genes, especially nirK gene, were more sensitive and stressed. Overall, phthalate esters originated from microplastics play a key role in nitrogen cycling-related functions than microplastics themselves, moreover, the synergy between di-n-octyl phthalate and copper strengthen the expression of denitrification functions.


Assuntos
Desnitrificação , Microplásticos , Microbiologia do Solo , Poluentes do Solo , Desnitrificação/efeitos dos fármacos , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Tibet , Microplásticos/toxicidade , Plastificantes/toxicidade , Plastificantes/metabolismo , Microbiota/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Metais Pesados/toxicidade
4.
ACS Med Chem Lett ; 15(2): 230-238, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38352836

RESUMO

Herein, we disclose a powerful strategy for the functionalization of the antitumor natural alkaloid noscapine by utilizing photoredox/nickel dual-catalytic coupling technology. A small collection of 37 new noscapinoids with diverse (hetero)alkyl and (hetero)cycloalkyl groups and enhanced sp3 character was thus synthesized. Further in vitro antiproliferative activity screening and SAR study enabled the identification of 6o as a novel, potent, and less-toxic anticancer agent. Furthermore, 6o exerts superior cellular activity via an unexpected S-phase arrest mechanism and could significantly induce cell apoptosis in a dose-dependent manner, thereby further highlighting its potential in drug discovery as a promising lead compound.

5.
Eur J Clin Microbiol Infect Dis ; 43(4): 713-721, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38347245

RESUMO

BACKGROUND AND AIM: Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA. METHODS: This retrospective case-control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed. RESULTS: Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367-17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively). CONCLUSIONS: Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA.


Assuntos
Doença Hepática Terminal , Aspergilose Pulmonar Invasiva , Humanos , Antifúngicos , Estudos Retrospectivos , Estudos de Casos e Controles , Glucocorticoides , Anfotericina B/uso terapêutico , Prognóstico , Fatores de Risco , Antibacterianos/uso terapêutico
6.
Food Funct ; 14(3): 1320-1337, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36722924

RESUMO

Exosomes are extracellular vesicles with the smallest diameter, usually divided into cellular sources and body fluid sources. Due to their special properties different from cell-derived exosomes, the application of milk exosomes as an oral drug delivery system has increased greatly. This article introduces the physical and chemical properties of exosomes, separation technology, dyeing and labeling technology, targeted modification technology, and the application of milk exosomes in drug loading and disease therapies.


Assuntos
Exossomos , Vesículas Extracelulares , Animais , Leite , Exossomos/química , Sistemas de Liberação de Medicamentos
7.
Foodborne Pathog Dis ; 16(5): 325-330, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30807231

RESUMO

Hepatitis E virus (HEV) is an important human pathogen with pigs serving as the main natural animal reservoir. In China, pork is the most popular meat, while pig viscera are also widely consumed. The aim of this study was to evaluate the prevalence of HEV among pigs at slaughter, and assess the presence of HEV in raw pork and pig viscera as food. Samples of pig blood, raw pork, liver, kidney, and blood curd were collected from slaughterhouse or (and) retail market. Anti-HEV antibody in serum samples was detected using enzyme-linked immunosorbent assay based on an ORF2 antigen sandwich kit. HEV RNA was tested by reverse transcription nested polymerase chain reaction (RT-nested PCR) and the viral load was further assessed using quantitative real-time PCR. The final amplicons of RT-nested PCR were sequenced and undergone phylogenetic analysis. Prevalence of antibodies to HEV was 90.4% (104/115) in pigs at slaughtered level, and one serum sample was HEV RNA positive (0.9%, 1/115). HEV RNA was detected in liver, kidney, and blood samples with positivity of 6.1% (7/114), 3.1% (4/129), and 1.2% (2/170) respectively with viral loads ranged 102.4-104.4 (2.4Log-4.4Log) genome equivalents per gram, but not in pork. The HEV RNA prevalence in both liver and kidney were statistically higher than in pork. Phylogenetic analysis showed that all obtained sequences belonged to HEV genotype 4, which were divided into subtypes 4a, 4b, 4d, and 4i, highly identical to the known human and swine HEV sequences in China. The results indicate that raw pig viscera are more likely to harbor HEV than pork, suggesting a higher transmission risk related to consuming pig organs.


Assuntos
Microbiologia de Alimentos , Vírus da Hepatite E/isolamento & purificação , Hepatite E/veterinária , Carne de Porco/virologia , Doenças dos Suínos/epidemiologia , Matadouros , Animais , Sangue/virologia , China/epidemiologia , Hepatite E/epidemiologia , Vírus da Hepatite E/genética , Rim/virologia , Limite de Detecção , Fígado/virologia , Filogenia , Prevalência , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Doenças dos Suínos/virologia
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