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1.
Nat Commun ; 15(1): 5287, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902231

RESUMO

Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains are conjugated to nanoparticles, for the targeted delivery of rifampicin, imipenem, and ampicillin against bacterial pathogens. They show excellent specificity against their targets, and accumulate at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppress pathogen infections more effectively than 16 to 32-fold higher doses of free antibiotics. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.


Assuntos
Antibacterianos , Bacteriófagos , Nanopartículas , Antibacterianos/administração & dosagem , Antibacterianos/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Proteínas Virais/metabolismo , Proteínas Virais/química , Animais , Camundongos , Rifampina/farmacologia , Rifampina/administração & dosagem , Humanos , Ampicilina , Infecções Bacterianas/tratamento farmacológico
2.
Mol Biomed ; 4(1): 37, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37907779

RESUMO

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, and represents a severe threat to the life and health of individuals. Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) as critical regulatory gene in cancer development. Small Cajal body-specific RNAs (scaRNAs), a subtype of snoRNAs, are named for their subcellular localization within Cajal bodies. SCARNA12, which located at the intronic region of PHB2 in chromosome 12p13.31 with 270 nucleotides (nt) in length. It has been reported function as a diagnostic marker for cervical cancer. However, its biological functions and molecular mechanisms in CRC have yet to be elucidated. In this study, bioinformatics analysis revealed that SCARNA12 was highly expressed in CRC and positively correlated with poor prognosis in CRC patients. Additionally, SCARNA12 showed upregulated expression in CRC cell lines and clinical CRC tissue samples. Moreover, SCARNA12 overexpression in SW620 cells accelerated cell proliferation, suppressed the apoptosis rate, and enhanced tumorigenesis in vivo. The knockdown of SCARNA12 expression in HCT116 and HT29 cells resulted in contrasting effects. The functioning of SCARNA12 is mechanically independent of its host gene PHB2. Notably, the overexpression of SCARNA12 activated PI3K/AKT pathway in SW620 cells, and the malignancy degree of CRC cells was attenuated after treatment with MK2206 (a specific AKT inhibitor). Our findings demonstrated that SCARNA12 plays an oncogenic role in CRC progression and can be used as a potential diagnostic biomarker for CRC.

3.
Front Microbiol ; 14: 1078430, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778848

RESUMO

Bacteria can facilitate the increase of Mg2+ content in biotic aragonite, but the molecular mechanisms of the incorporation of Mg2+ ion into aragonite facilitated by bacteria are still unclear and the dolomitization of aragonite grains is rarely reported. In our laboratory experiments, the content of Mg2+ ions in biotic aragonite is higher than that in inorganically-precipitated aragonite and we hypothesize that the higher Mg content may enhance the subsequent dolomitization of aragonite. In this study, biotic aragonite was induced by Bacillus licheniformis Y1 at different Mg/Ca molar ratios. XRD data show that only aragonite was precipitated in the media with Mg/Ca molar ratios at 6, 9, and 12 after culturing for 25 days. The EDS and atomic absorption results show that the content of Mg2+ ions in biotic aragonite increased with rising Mg/Ca molar ratios. In addition, our analyses show that the EPS from the bacteria and the organics extracted from the interior of the biotic aragonite contain the same biomolecules, including Ala, Gly, Glu and hexadecanoic acid. The content of Mg2+ ions in the aragonite precipitates mediated by biomolecules is significantly higher than that in inorganically-precipitated aragonite. Additionally, compared with Ala and Gly, the increase of the Mg2+ ions content in aragonite promoted by Glu and hexadecanoic acid is more significant. The DFT (density functional theory) calculations reveal that the energy needed for Mg2+ ion incorporation into aragonite mediated by Glu, hexadecanoic acid, Gly and Ala increased gradually, but was lower than that without acidic biomolecules. The experiments also show that the Mg2+ ion content in the aragonite significantly increased with the increasing concentration of biomolecules. In a medium with high Mg2+ concentration and with bacteria, after 2 months, micron-sized dolomite rhombs were precipitated on the surfaces of the aragonite particles. This study may provide new insights into the important role played by biomolecules in the incorporation of the Mg2+ ions into aragonite. Moreover, these experiments may contribute towards our understanding of the dolomitization of aragonite in the presence of bacteria.

4.
Infect Dis Poverty ; 4: 53, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26653890

RESUMO

BACKGROUND: The prevalence of infection with Toxoplasma gondii (T. gondii) in humans has been increasing in China due to the growing number of cats in the country. Hand, foot and mouth disease (HFMD) is a serious public health issue in China and still one of the leading causes of child mortality. However, little is known about the epidemiology of T. gondii infection among HFMD patients. METHODS: A case-control study of 281 HFMD patients from the First People's Hospital of Pingdingshan in Pingdingshan city, Henan province, central China, and 222 controls from Pingdingshan city was conducted. Anti-T. gondii antibodies were serologically detected using the enzyme-linked immunosorbent assay. RESULTS: We found that the overall anti-T. gondii immunoglobulin G (IgG) antibody prevalence among HFMD patients was 12.46 %, which was significantly higher than that in clinically healthy children (1.80 %). The highest T. gondii seroprevalence was detected in critical cases (22.58 %), followed by severe cases (11.50 %), and the lowest was detected in mild cases (8.33 %). CONCLUSION: The present study is the first survey of T. gondii seroprevalence among HFMD patients in China; 12.46 % were defined as seropositive. It is imperative that improved integrated measures are taken to prevent and control T. gondii infection among HFMD patients.


Assuntos
Coinfecção , Doença de Mão, Pé e Boca/epidemiologia , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Toxoplasmose/parasitologia , Animais , Anticorpos Antiprotozoários , Estudos de Casos e Controles , Gatos , Criança , Pré-Escolar , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitalização , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , Prevalência , Estudos Soroepidemiológicos , Índice de Gravidade de Doença , Toxoplasmose/diagnóstico
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