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1.
Antimicrob Agents Chemother ; : e0005424, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687016

RESUMO

Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol, and impaired the polymerase activity of 3D pol, hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our findings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.

2.
Environ Sci Technol ; 57(33): 12137-12152, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37578142

RESUMO

Microorganisms colonizing the surfaces of microplastics form a plastisphere in the environment, which captures miscellaneous substances. The plastisphere, owning to its inherently complex nature, may serve as a "Petri dish" for the development and dissemination of antibiotic resistance genes (ARGs), adding a layer of complexity in tackling the global challenge of both microplastics and ARGs. Increasing studies have drawn insights into the extent to which the proliferation of ARGs occurred in the presence of micro/nanoplastics, thereby increasing antimicrobial resistance (AMR). However, a comprehensive review is still lacking in consideration of the current increasingly scattered research focus and results. This review focuses on the spread of ARGs mediated by microplastics, especially on the challenges and perspectives on determining the contribution of microplastics to AMR. The plastisphere accumulates biotic and abiotic materials on the persistent surfaces, which, in turn, offers a preferred environment for gene exchange within and across the boundary of the plastisphere. Microplastics breaking down to smaller sizes, such as nanoscale, can possibly promote the horizontal gene transfer of ARGs as environmental stressors by inducing the overgeneration of reactive oxygen species. Additionally, we also discussed methods, especially quantitatively comparing ARG profiles among different environmental samples in this emerging field and the challenges that multidimensional parameters are in great necessity to systematically determine the antimicrobial dissemination risk in the plastisphere. Finally, based on the biological sequencing data, we offered a framework to assess the AMR risks of micro/nanoplastics and biocolonizable microparticles that leverage multidimensional AMR-associated messages, including the ARGs' abundance, mobility, and potential acquisition by pathogens.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana/genética , Microplásticos , Plásticos , Transferência Genética Horizontal
3.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2426-2434, 2023 May.
Artigo em Zh | MEDLINE | ID: mdl-37282872

RESUMO

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.


Assuntos
Glicosídeos Cardíacos , Disfunção Cognitiva , Camundongos , Animais , Tripterygium , Lipossomos , Glicosídeos/uso terapêutico , Administração Intranasal , Lipopolissacarídeos , Sistema Nervoso Central , Disfunção Cognitiva/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
J Craniofac Surg ; 33(1): 354-359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34292250

RESUMO

ABSTRACT: Reconstruction of peripheral nerve injury remains a challenge for clinical medicine. Previous reports have confirmed that external oblique muscle-fabricated nerve conduit (EMC) could effectively be used to promote peripheral nerve regeneration. In this study, we compared between conduits fabricated from fresh muscle and conduits fabricated from predegenerated muscle for the repair of peripheral nerve defects in a mouse sciatic nerve transection model. We found that the number, diameter, and myelin sheath thickness of the myelinated nerve fibers of the regenerative nerve in the EMC group were larger than those of the predegenerated-EMC (P-EMC) group eight weeks after surgery. The sciatic function index and gastrocnemius wet-weight mass ratio in the EMC group were higher than those in the P-EMC group. The Bcl-2/Bax ratio and the number of Schwann cell nucleus in the proximal nerve stumps in the EMC group were greater than those in the P-EMC group. In conclusion, our results confirmed that the use of fresh skeletal muscle nerve conduit increased the Bcl-2/Bax ratio and promoted the survival of Schwann cells of the proximal nerve stump compared with that of predegenerated skeletal muscle nerve conduits, thus achieving better functional recovery after sciatic nerve defect.


Assuntos
Implantes Dentários , Traumatismos dos Nervos Periféricos , Animais , Camundongos , Músculo Esquelético , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/cirurgia , Células de Schwann , Nervo Isquiático/cirurgia
5.
Int J Mol Sci ; 22(21)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34769299

RESUMO

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.


Assuntos
Antivirais/farmacologia , Hidroxicolesteróis/química , Lipopeptídeos/química , SARS-CoV-2/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antivirais/química , Antivirais/uso terapêutico , Peso Corporal/efeitos dos fármacos , COVID-19/virologia , Coronavirus Humano 229E/efeitos dos fármacos , Coronavirus Humano 229E/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Coronavirus Humano OC43/efeitos dos fármacos , Coronavirus Humano OC43/patogenicidade , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Hidroxicolesteróis/farmacologia , Hidroxicolesteróis/uso terapêutico , Lipopeptídeos/farmacologia , Lipopeptídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Taxa de Sobrevida , Internalização do Vírus/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
6.
BMC Oral Health ; 20(1): 316, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172456

RESUMO

BACKGROUND: To investigate the effects of Er:YAG laser pre-treatment on the dentin structure and shear bond strength of primary teeth. METHODS: Dentin specimens were prepared using freshly extracted intact primary molars and divided randomly into four groups based on the surface treatment applied. The control and etchant groups received no treatment and conventional acid etching treatment, respectively, while the energy and frequency groups received laser surface treatment with variable energy (50-300 mJ) and frequency (5-30 Hz) parameters. The morphology was observed using scanning electron microscopy. The surface-treated dentin slices were bonded to resin tablets, followed by thermocycle treatment. The shear strength was determined using a universal testing machine and de-bonded surfaces were observed using a stereomicroscope. RESULTS: SEM observation showed that the surface morphology of the dentin slices changed after etching as well as after Er:YAG laser pre-treatment with different energy and frequency values. The dentin tubules opened within a specific energy (50-200 mJ) and frequency (5-20 Hz) range. Beyond this range, the intertubular dentin showed cracks and structural disintegration. Shear strength tests showed no significant changes after acid etching. The shear strength increased significantly (P < 0.05) after Er:YAG laser pre-treatment compared with that of the control group. The shear strength increased within the same energy (50-200 mJ) and frequency (5-20 Hz) range as the tubule opening, but not significantly (P > 0.05). The most common mode of interface failure was adhesive (interface) failure, followed by mixed and resin cohesive failure. CONCLUSIONS: Pre-treatment using Er:YAG laser opens the dentinal tubules without the formation of a smear layer and improves the bonding strength between the primary teeth dentin and the resin composites.


Assuntos
Colagem Dentária , Lasers de Estado Sólido , Cimentos Dentários , Dentina , Humanos , Lasers de Estado Sólido/uso terapêutico , Microscopia Eletrônica de Varredura , Cimentos de Resina , Resistência ao Cisalhamento , Dente Decíduo
7.
Electrophoresis ; 39(2): 356-362, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29067704

RESUMO

In this work, a simple and rapid approach was developed for separation and detection of chiral compounds based on a magnetic molecularly imprinted polymer modified poly(dimethylsiloxane) (PDMS) microchip coupled with electrochemical detection. Molecularly imprinted polymers were prepared employing Fe3 O4 nanoparticles (NPs) as the supporting substrate and norepinephrine as the functional monomer in the presence of template molecule in a weak alkaline solution. After extracting the embedded template molecules, Fe3 O4 @polynorepinephrine NPs (MIP-Fe3 O4 @PNE NPs) showed specific molecular recognition selectivity and high affinity towards the template molecule, which were then used as stationary phase of microchip capillary electrochromatography for chiral compounds separation. Mandelic acid and histidine enantiomers were used as model compounds to test the chiral stationary phase. By using R-mandelic acid as the template molecule, mandelic acid enantiomer was effectively separated and detected on the MIP-Fe3 O4 @PNE NPs modified PDMS microchip. Moreover, the successful separation of histidine enantiomers on the MIP-Fe3 O4 @PNE NPs modified microchip using L-histidine as template molecule was also achieved.


Assuntos
Eletrocromatografia Capilar/métodos , Nanopartículas de Magnetita/química , Impressão Molecular/métodos , Eletro-Osmose , Histidina/química , Limite de Detecção , Ácidos Mandélicos/química , Norepinefrina/química , Polímeros/química , Reprodutibilidade dos Testes , Estereoisomerismo
8.
Drug Dev Ind Pharm ; 44(4): 563-569, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29148846

RESUMO

OBJECTIVE: Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin's solubility and thus oral bioavailability. METHODS: Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats. KEY FINDINGS: The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin's oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin. CONCLUSIONS: The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability.


Assuntos
Curcumina/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Disponibilidade Biológica , Células CACO-2 , Sobrevivência Celular , Curcumina/química , Curcumina/farmacocinética , Composição de Medicamentos , Excipientes , Humanos , Micelas , Polietilenoglicóis , Polivinil , Ratos , Ratos Sprague-Dawley , Solubilidade , Solventes
9.
Crit Care Med ; 44(11): e1090-e1096, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27760056

RESUMO

OBJECTIVES: To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model. SETTING: Laboratory. SUBJECTS: Male Wistar rats. DESIGN: Prospective study. INTERVENTIONS: Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids. MEASUREMENTS AND MAIN RESULTS: The mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability. CONCLUSIONS: Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.


Assuntos
Ressuscitação/métodos , Albumina Sérica/farmacologia , Choque Hemorrágico/tratamento farmacológico , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Quimiocina CCL2/sangue , Citocinas/metabolismo , Pulmão/metabolismo , Lesão Pulmonar/prevenção & controle , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Polietilenoglicóis/química , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Traumatismo por Reperfusão/prevenção & controle , Albumina Sérica/química , Proteína X Associada a bcl-2/metabolismo
10.
Electrophoresis ; 37(12): 1676-84, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26970233

RESUMO

In this paper, using the self-polymerization of norepinephrine (NE) and its favorable film-forming property, a simple and green preparation approach was developed to modify a PDMS channel for enantioseparation of chiral compounds. After the PDMS microchip was filled with NE solution, poly(norepinephrine) (PNE) film was gradually formed and deposited on the inner wall of microchannel as permanent coating via the oxidation of NE by the oxygen dissolved in the solution. Due to possessing plentiful catechol and amine functional groups, the PNE-coated PDMS microchip exhibited much better wettability, more stable and suppressed EOF, and less nonspecific adsorption. The water contact angle and EOF of PNE-coated PDMS substrate were measured to be 13° and 1.68 × 10(-4) cm(2) V(-1) s(-1) , compared to those of 108° and 2.24 × 10(-4) cm(2) V(-1) s(-1) from the untreated one, respectively. Different kinds of chiral compounds, such as amino acid enantiomer, drug enantiomer, and peptide enantiomer were efficiently separated utilizing a separation length of 37 mm coupled with in-column amperometric detection on the PNE-coated PDMS microchips. This facile mussel-inspired PNE-based microchip system exhibited strong recognition ability, high-performance, admirable reproducibility, and stability, which may have potential use in the complex biological analysis.


Assuntos
Eletroforese em Microchip/métodos , Norepinefrina/metabolismo , Animais , Bivalves , Dimetilpolisiloxanos , Eletroforese em Microchip/instrumentação , Química Verde , Polimerização , Reprodutibilidade dos Testes , Estereoisomerismo
11.
Molecules ; 21(4): 511, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27110762

RESUMO

This study aimed to determine the influence of different emulsifiers or xanthan-emulsifier systems on the release of aroma compounds. Solid-phase microextraction (SPME) and GC-MS were used to study the effects of varying concentrations of xanthan gum, sucrose fatty acid ester, Tween 80 and soybean lecithin on the release of seven aroma compounds. The effects of the emulsifier systems supplemented with xanthan gum on aroma release were also studied in the same way. The results showed varying degrees of influence of sucrose fatty acid ester, soybean lecithin, Tween 80 and xanthan gum on the release of aroma compounds. Compared with other aroma compounds, ethyl acetate was more likely to be conserved in the solution system, while the amount of limonene released was the highest among these seven aroma compounds. In conclusion, different emulsifiers and complexes showed different surface properties that tend to interact with different aroma molecules. The present studies showed that the composition and structure of emulsifiers and specific interactions between emulsifiers and aroma molecules have significant effects on aroma release.


Assuntos
Emulsificantes/química , Aditivos Alimentares/química , Glycine max/química , Odorantes/análise , Indústria de Processamento de Alimentos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Lecitinas/química , Polissacarídeos Bacterianos/química , Polissorbatos/química , Microextração em Fase Sólida/métodos , Sacarose/química , Propriedades de Superfície
12.
Water Environ Res ; 96(7): e11080, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38970489

RESUMO

The presence of perfluoroalkyl substances (PFAS) in the environment poses a significant threat to ecological safety and environmental health. Widespread microplastics (MPs) have been recognized as vectors for emerging contaminants due to human activities. However, the adsorption behaviors of PFAS on MPs, especially on aged MPs, have not been extensively investigated. This study aimed to investigate the adsorption behaviors of perfluorooctanoic acid (PFOA) on aged MPs (polystyrene, polyethylene, and polyethylene terephthalate) treated with UV irradiation and persulfate oxidation under salinity and dissolve organic matter (DOM) condition. Carbonyl index values of MPs increased after the aged treatment, indicating the production of oxygen-containing groups. The PFOA adsorption on aged MPs was impacted by the co-existence of Na+ ions and DOM. As PFOA adsorption onto aged MPs was mainly controlled by hydrophobic interaction, the electrostatic interaction also made a contribution, but there was no significant change in PFOA adsorption behavior between the pristine and aged MPs. While these findings provide insight into PFAS adsorption on aged MPs, further research is necessary to account for the complexity of the real environment. PRACTITIONER POINTS: Adsorption behaviors of perfluorooctanoic acid (PFOA) on aged microplastics were investigated. Hydrophobic interaction mainly controlled PFOA adsorption on aged microplastics (MPs). Co-existence dissolve organic matter and salinity influenced PFOA adsorption behaviors on aged MPs.


Assuntos
Caprilatos , Fluorocarbonos , Microplásticos , Poluentes Químicos da Água , Fluorocarbonos/química , Caprilatos/química , Microplásticos/química , Adsorção , Poluentes Químicos da Água/química
13.
Environ Int ; 185: 108532, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422876

RESUMO

Nanoplastics (NPs) continue to accumulate in global aquatic and terrestrial systems, posing a potential threat to human health through the food chain and/or other pathways. Both in vivo and in vitro studies have confirmed that the liver is one of the main organs targeted for the accumulation of NPs in living organisms. However, whether exposure to NPs induces size-dependent disorders of liver lipid metabolism remains controversial, and the reversibility of NPs-induced hepatotoxicity is largely unknown. In this study, the effects of long-term exposure to environmentally relevant doses of polystyrene nanoplastics (PS-NPs) on lipid accumulation were investigated in terms of autophagy and lysosomal mechanisms. The findings indicated that hepatic lipid accumulation was more pronounced in mice exposed to 100 nm PS-NPs compared to 500 nm PS-NPs. This effect was effectively alleviated after 50 days of self-recovery for 100 nm and 500 nm PS-NPs exposure. Mechanistically, although PS-NPs exposure activated autophagosome formation through ERK (mitogen-activated protein kinase 1)/mTOR (mechanistic target of rapamycin kinase) signaling pathway, the inhibition of Rab7 (RAB7, member RAS oncogene family), CTSB (cathepsin B), and CTSD (cathepsin D) expression impaired lysosomal function, thereby blocking autophagic flux and contributing to hepatic lipid accumulation. After termination of PS-NPs exposure, lysosomal exocytosis was responsible for the clearance of PS-NPs accumulated in lysosomes. Furthermore, impaired lysosomal function and autophagic flux inhibition were effectively alleviated. This might be the main reason for the alleviation of PS-NPs-induced lipid accumulation after recovery. Collectively, we demonstrate for the first time that lysosomes play a dual role in the persistence and reversibility of hepatotoxicity induced by environmental relevant doses of NPs, which provide novel evidence for the prevention and intervention of liver injury associated with nanoplastics exposure.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Nanopartículas , Poluentes Químicos da Água , Humanos , Animais , Camundongos , Microplásticos , Poliestirenos/toxicidade , Lisossomos , Lipídeos
14.
Front Microbiol ; 15: 1402807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800748

RESUMO

Pigs are widely used as animal models in various studies related to humans. The interaction between the gut microbiota and the host has significant effects on the host's health and disease status. However, although there have been many studies investigating the pig gut microbiota, the findings have been inconsistent due to variations in rearing conditions. Interactions between the gut microbiota and host have not been fully explored in pigs. Specific pathogen-free (SPF) pigs are ideal non-primate large animals to study the interactions between the gut microbiota and the host. In this study, we performed high-throughput sequencing analysis of the gut microbiota and the gut tissue transcriptome of six SPF pigs to provide a systematic understanding of the composition, function, and spatial distribution of gut microbiota in SPF pigs. We identified significant differences in microbial diversity and functionality among different gastrointestinal tract sites. Metagenomics data analysis revealed significant differences in alpha diversity and beta diversity of microbiota in different gastrointestinal sites of SPF pigs. Additionally, transcriptomic data indicated significant differences in gene expression as well as KEGG and GO functional enrichment between the small intestine and large intestine. Furthermore, by combining microbial metagenomics and host transcriptomics analyses, specific correlations were found between gut microbiota and host genes. These included a negative correlation between the TCN1 gene and Prevotella dentalis, possibly related to bacterial metabolic pathways involving vitamin B12, and a positive correlation between the BDH1 gene and Roseburia hominis, possibly because both are involved in fatty acid metabolism. These findings lay the groundwork for further exploration of the co-evolution between the microbiota and the host, specifically in relation to nutrition, metabolism, and immunity. In conclusion, we have elucidated the diversity of the gut microbiota in SPF pigs and conducted a detailed investigation into the interactions between the gut microbiota and host gene expression. These results contribute to our understanding of the intricate dynamics between the gut microbiota and the host, offering important references for advancements in life science research, bioproduct production, and sustainable development in animal husbandry.

15.
Anal Chim Acta ; 1312: 342762, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38834277

RESUMO

Mucin1 (MUC1) is an extensively glycosylated transmembrane protein that is widely distributed and overexpressed on the surface of cancer cells, playing an important role in tumor occurrence and metastasis. Therefore, highly sensitive detection of MUC1 is of great significance for early diagnosis, treatment monitoring, and prognosis of cancer. Here, an ultra-sensitive photoelectrochemical (PEC) sensing platform was developed based on an aptamer amplification strategy for highly selective and sensitive detection of MUC1 overexpressed in serum and on cancer cell surfaces. The sensing platform utilized copper phthalocyanine to fabricate porous organic polymers (CuPc POPs), and was effectively integrated with g-C3N4/MXene to form a ternary heterojunction material (g-C3N4/MXene/CuPc POPs). This material effectively improved electron transfer capability, significantly enhanced light utilization, and greatly enhanced photoelectric conversion efficiency, resulting in a dramatic increase in photocurrent response. MUC1 aptamer 1 was immobilized on a chitosan-modified photoelectrode for the selective capture of MUC1 or MCF-7 cancer cells. When the target substance was present, MUC1 aptamer 2 labeled with methylene blue (MB) was specifically adsorbed on the electrode surface, leading to enhanced photocurrent. The concentration of MUC1 directly correlated with the number of MB molecules attracted to the electrode surface, establishing a linear relationship between photocurrent intensity and MUC1 concentration. The PEC biosensor exhibited excellent sensitivity for MUC1 detection with a wide detection range from 1 × 10-7 to 10 ng/mL and a detection limit of 8.1 ag/mL. The detection range for MCF-7 cells was from 2 × 101 to 2 × 106 cells/mL, with the capability for detecting single MCF-7 cells. The aptamer amplification strategy significantly enhanced PEC performance, and open up a promising platform to establish high selectivity, stability, and ultrasensitive analytical techniques.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Eletroquímicas , Mucina-1 , Polímeros , Mucina-1/análise , Humanos , Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Células MCF-7 , Porosidade , Polímeros/química , Limite de Detecção , Técnicas Biossensoriais/métodos , Indóis/química , Processos Fotoquímicos , Compostos Organometálicos/química
16.
Front Neurol ; 15: 1319962, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481944

RESUMO

This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.

17.
Mol Genet Genomic Med ; 12(3): e2405, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444283

RESUMO

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.


Assuntos
Disostose Mandibulofacial , Infecções Respiratórias , Feminino , Humanos , China , Perda Auditiva Condutiva , Disostose Mandibulofacial/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Estudos Retrospectivos
18.
Adv Sci (Weinh) ; 11(24): e2306675, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647399

RESUMO

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.


Assuntos
Doença de Alzheimer , Barreira Hematoencefálica , Modelos Animais de Doenças , Lipossomos , Camundongos Transgênicos , Nanopartículas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Camundongos , Nanopartículas/química , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Humanos
19.
Opt Express ; 21(6): 7133-8, 2013 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-23546096

RESUMO

The surface localized polymer alignment (SLPA) method allows complete control of the polar pretilt angle as a function of position in liquid crystal devices. In this work, a liquid crystal (LC) cylindrical lens is fabricated by the SLPA method. The focal length of the LC lens is set by the polymerization conditions, and can be varied by a non-segmented electrode. The LC lens does not require a shaped substrate, or complicated electrode patterns, to achieve a desired parabolic phase profile. Therefore, both fabrication and driving process are relatively simple.


Assuntos
Eletrodos , Lentes , Cristais Líquidos/química , Cristais Líquidos/efeitos da radiação , Refratometria/instrumentação , Campos Eletromagnéticos , Desenho de Equipamento , Análise de Falha de Equipamento , Teste de Materiais , Conformação Molecular , Polímeros/química , Polímeros/efeitos da radiação , Propriedades de Superfície/efeitos da radiação
20.
BMC Infect Dis ; 13: 539, 2013 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-24225231

RESUMO

BACKGROUND: We investigated the epidemiological and clinical data of all hand, foot, and mouth disease (HFMD) cases in a sentinel hospital of Shenzhen, China from 2009 to 2011. METHODS: HFMD cases diagnosed in our institution were assessed from 2009 to 2011. Both epidemiological and clinical features were analyzed retrospectively. All the fatal cases were reported. RESULTS: A total of 12132 patients were diagnosed with HFMD, of which 2944 (24.3%) were hospitalized. Of the 2944 hospitalized patients, the highest proportion of diagnosed cases were admitted in May and July (989/2944, 33.6%). In 2009 all severe HFMD cases were diagnosed with enterovirus 71 (EV71). In 2010 and 2011, some of the severe HFMD were diagnosed with Coxsackievirus A16 (CA16). Incidence was highest in 0-4-year old children, with males being predominant. There were sporadic cases with HFMD the whole year except in February. All cases were cured in 2009. Six deaths were reported during 2010 and 2011. CONCLUSIONS: EV71 can cause severe complications and deaths in our region. HFMD is an important public health problem in Shenzhen in spite of stringent measures taken in preschool centers. A high degree of vigilance should be maintained over the disease situation.


Assuntos
Doença de Mão, Pé e Boca/diagnóstico , Doença de Mão, Pé e Boca/epidemiologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Feminino , Doença de Mão, Pé e Boca/virologia , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Estudos Retrospectivos
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