Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
1.
BMC Ophthalmol ; 22(1): 234, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606707

RESUMO

BACKGROUND: To compare the quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy (TPRK) and off-flap epipolis-laser in situ keratomileusis (Epi-LASIK) in moderate to high myopia. METHODS: In this prospective self-control study, we included patients with moderate to high myopia who were randomized to undergo TPRK in one eye and Epi-LASIK in the other eye. Twelve-month follow-up results for visual acuity, refraction, ocular high-order aberrations, contrast sensitivity, postoperative pain, epithelial healing, and haze grade were assessed. RESULTS: A total of 64 eyes (32 patients) were enrolled in the study. More eyes completed re-epithelialization in the TPRK group than in the Off-flap Epi-LASIK group 3-4 days postoperatively, while all eyes completed re-epithelialization by 7 days. More eyes achieved a visual acuity (both UDVA and CDVA) of better than 20/20 in the TPRK group than in the Off-flap Epi-LASIK group. The ±0.50 D predictability for correction of the spherical equivalent (SE) was higher in the eyes of the TPRK group (91%) than in those of the off-flap Epi-LASIK group (80%) 12 months after surgery. No significant differences in ocular aberrations, including coma, spherical, and trefoil, were found between the two groups at 12 months. There were also no significant differences in visual acuity, contrast sensitivity, pain, and haze grading between the two groups. CONCLUSIONS: Both TPRK and off-flap Epi-LASIK are safe, effective, and predictable treatments for moderate to high myopia with comparable surgical outcomes. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrial.gov ( NCT05060094 , 17/09/2021).

2.
Adv Healthc Mater ; : e2200400, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35485404

RESUMO

Nitroreductase (NTR), a common enzymatic biomarker of hypoxia, is widely used to evaluate tumor microenvironments. To date, numerous optical probes have been reported for NTRs detection. Approaches capable of concisely guiding the probe design of NTRs suitable for deep-tissue imaging, however, are still lacking. As such, direct optical imaging of endogenous NTR activities from tumors derived from cancer patients is thus far not possible. Herein, aided by computational calculations, the authors have successfully developed a series of two-photon (TP) small-molecule fluorogenic probes capable of sensitively detecting general NTR activities from various biological samples; by optimizing the distance between the recognition moiety and the reactive site of NTRs from different sources, the authors have discovered and experimentally proven that X4 displays the best performance in both sensitivity and selectivity. Furthermore, X4 shows excellent TP excited fluorescence properties capable of directly monitoring/imaging endogenous NTR activities from live mammalian cells, growing zebrafish, and tumor-bearing mice. Finally, with an outstanding TP tissue-penetrating imaging property, X4 is used, for the first time, to successfully detect endogenous NTR activities from the liver lysates and cardia tissues of a cancer patient. The work may provide a universal strategy to design novel TP small-molecule enzymatic probes in future clinical applications.

3.
Genome Instab Dis ; 3(2): 83-87, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252763

RESUMO

The ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR) are apical kinases that orchestrate the multifaceted DNA damage response (DDR) to a variety of genotoxic insults and regulate genomic stability. Whether RNA virus also manipulates the host's DDR machine to facilitate replication is largely unknown. In this study, we revealed that single-stranded RNA virus replication specifically elicits host ATM- and ATR-mediated pathway activation and boosts their expression. The activated ATM and ATR are hijacked to the virus replication factory in the cytoplasm and facilitate viral gene expression and replication. Specific inhibitors targeting ATM and ATR strikingly block the viral proliferation and replication and inhibit expression of virus proteins. Our results reveal a novel, or otherwise noncanonical, conserved function of ATM/ATR outside DDR in promoting the replication of single-stranded RNA virus and provide an important mechanism of host-pathogen interactions. Supplementary Information: The online version contains supplementary material available at 10.1007/s42764-022-00064-3.

4.
Mol Cell ; 82(4): 770-784.e9, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35114100

RESUMO

The mTOR complex 1 (mTORC1) is an essential metabolic hub that coordinates cellular metabolism with the availability of nutrients, including amino acids. Sestrin2 has been identified as a cytosolic leucine sensor that transmits leucine status signals to mTORC1. In this study, we identify an E3 ubiquitin ligase RING finger protein 167 (RNF167) and a deubiquitinase STAMBPL1 that function in concert to control the polyubiquitination level of Sestrin2 in response to leucine availability. Ubiquitination of Sestrin2 promotes its interaction with GATOR2 and inhibits mTORC1 signaling. Bioinformatic analysis reveals decreased RNF167 expression and increased STAMBPL1 expression in gastric and colorectal tumors. Knockout of STAMBPL1 or correction of the heterozygous STAMBPL1 mutation in a human colon cancer cell line suppresses xenograft tumor growth. Lastly, a cell-permeable peptide that blocks the STAMBPL1-Sestrin2 interaction inhibits mTORC1 and provides a potential option for cancer therapy.


Assuntos
Neoplasias Colorretais/enzimologia , Peptídeo Hidrolases/metabolismo , Neoplasias Gástricas/enzimologia , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Células CACO-2 , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HEK293 , Humanos , Leucina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação , Proteínas Nucleares/metabolismo , Peptídeo Hidrolases/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Carga Tumoral , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
5.
Food Chem ; 380: 132188, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35077990

RESUMO

A simple and high-throughput colorimetric analysis array has been constructed for quantifying H2O2 in milk using Fe3O4 quantum dots (QDs), which were coated with sodium alginate (SA) and chromogenic substrate onto the arrayed capillary tubes. It was discovered that the Fe3O4 QDs could present larger peroxidase-like catalysis than Fe3O4 nanoparticles (NPs). Particularly, dramatically enhanced catalysis activity could be achieved for Fe3O4 QDs if coated with SA films. Moreover, the use of SA could protect Fe3O4 QDs to expect the improved environmental stability. A capillary arrays-based high-throughput colorimetric platform was thereby developed for the detection of H2O2 in milk, with levels linearly ranging from 10 to 400 µM. Importantly, the developed colorimetric platform with the capillarity power for automatic fetching of multiple samples may promise the practical applications for extensive monitoring of multiple H2O2 samples for food safety.


Assuntos
Pontos Quânticos , Alginatos , Animais , Catálise , Colorimetria , Peróxido de Hidrogênio/análise , Leite/química
6.
Animals (Basel) ; 11(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34944292

RESUMO

The purpose of this study was to evaluate the effects of dietary supplementation with microalgae (Schizochytrium sp.) containing docosahexaenoic acid (DHA) on the antioxidant enzyme activity, physicochemical quality, fatty acid composition and volatile compounds of beef meat. Eighteen male Qaidamford cattle were randomly allocated into three treatments (n = 6): no micro-algae supplementation (Control group, C), 100 g microalgae supplementation per bull per day (FD1), and 200 g microalgae supplementation per bull per day (FD2), and fed for 49 days before slaughter. The results showed that, compared with the C group, the addition of DHA-rich microalgae to the diet could significantly increase the total antioxidant capacity (T-AOC) in meat. In the FD2 group, it was found that the concentration of glutathione peroxidase (GSH-Px) was significantly higher than that of the control group (p < 0.05). DHA-rich microalgae supplementation increased polyunsaturated fatty acid (PUFA), eicosapentaenoic acid (EPA; C20:5 n-6), DHA, EPA + DHA, and n-3 PUFA and reduced n-6:n-3 fatty acid ratio. Twenty-four volatile compounds identified in beef were mainly aldehydes, alcohols and ketones from the fingerprints. The contents of short-chain fatty aldehydes, 1-octen-3-ol and 2-pentylfuran, were higher in the FD2 group than in the other two groups. The microalgae diet improved the sensory attribute score of beef. The results demonstrated that dietary supplementation of DHA-rich microalgae improved the antioxidant status, increased the deposition of DHA and enhanced the characteristic flavor of beef.

7.
Sci Rep ; 11(1): 21676, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737361

RESUMO

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25-1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.


Assuntos
Colistina/uso terapêutico , Ácido Edético/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/tratamento farmacológico , Cateteres/microbiologia , Colistina/metabolismo , Combinação de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Virulência
8.
J Environ Manage ; 298: 113474, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364244

RESUMO

China is the second largest irrigated country in the world. Increasing irrigation intensity costs more water and energy, and produces more greenhouse gas (GHG). In the present study, the responses of maize economic and environmental benefits to different irrigation managements were analyzed in a 2-year field study. A purposely designed tube-study was conducted to explore mechanism underlying effects of irrigation managements in detail. Three treatments, rainfed (RF), flood irrigation (FI), and drip irrigation (DI) were included in the field. Five treatments, no irrigation, flood irrigation, irrigation in 0-30, 30-60, and 0-90 cm depth were conducted in the tube study. Compared to RF, grain yields of FI and DI significantly increased by 22.1 % and 35.7 %, respectively, the net ecosystem economic budget significantly increased by 34.2 % and 35.6 %, and carbon footprint decreased by 7.0 % and 12.7 % in the field study. The irrigation treatments in the tube study increased the global warming potential by 12.0-32.8 % and grain yield by 44.5-203.9 %, and reduced GHG intensity by 24.3-57.4 %, compared with no irrigation treatment. Water content at the top soil layer had the greatest impact on GHG emissions. In conclusion, the differences in grain yield and GHG emissions among irrigation managements are mainly due to the soil water content in space and time. Drip irrigation decreases GHG intensity by producing more grain yield due to the optimized soil water distribution in the root zone. Irrigation management with appropriate amount and frequency can increase economic benefit and reduce environmental cost in maize production.


Assuntos
Aquecimento Global , Zea mays , Irrigação Agrícola , Agricultura , China , Ecossistema , Óxido Nitroso/análise , Solo
9.
Front Microbiol ; 12: 642959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421832

RESUMO

Current information on the differences between rumen bacteria and metabolites of the grass-fed and grain-fed yaks is limited. Understanding the composition and alterations of rumen microbial metabolites is important to clarify its potential role in grass-fed and grain-fed systems. The aim of this research was to explore the influence of different production systems on the functional attributes and metabolites in the rumen microbiota of yak using genomics (Illumina MiSeq sequencing of the 16S rRNA gene) and untargeted metabolomics (UHPLC-QTOF-MS). Rumen samples were obtained from grass-fed (C), grain-fed for 3-month (G3), and grain-fed for 6-month yaks (G6). Results showed that the grain-fed yaks presented a lower rumen bacterial richness and diversity when compared to grass-fed yaks. Bacteroidota, Firmicutes, and Fibrobacterota were the main bacterial phyla. At the phylum and genus level, the grass-fed yaks significantly increased the abundance of Fibrobacterota and Fibrobacter (p < 0.05), respectively. The metabolomics analysis revealed that the metabolite profiles differed among the three groups. Compared with the grass-fed group, grain feeding significantly increased azelaic acid, hypoxanthine, uridine, L-phenylalanine, anserine, and decreased alpha-linolenic acid, adenine. Pathway enrichment analysis showed significant differences in metabolic pathways among all comparison groups, but the glycerophospholipid metabolism and alpha-linolenic acid metabolism pathway were common key metabolic pathways. This study showed that the combined analysis of microbiota and metabolites could distinguish different production systems and the fattening time of yaks, providing novel insights for us to understand the function of the rumen bacteria.

10.
J Mater Chem B ; 9(30): 5998-6005, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34259306

RESUMO

A high-throughput and selective fluorimetric platform has been constructed for the analysis of ammonia in blood by using a polymer-stabilized metal-organic framework (MOF) of porous NH2-MIL-125, which was coated onto a wettable microwells array constructed on an indium tin oxide (ITO) substrate. It was found that the nitrogen plasma treatment for the ITO substrate could create a super-hydrophilic interface that combined with the hydrophobic pattern yielded a wettable microwells array, enabling the condensation-based enrichment of targets from the sample droplets. Moreover, the NH2-MIL-125 MOF encapsulated using polymers could be firmly coated onto the microwells to act as fluorescent probes for sensing NH3 with enhanced responses. In addition, the use of the polymer polyvinyl pyrrolidone could protect and stabilize the crystals of NH2-MIL-125 probe in aqueous media, revealing the improved hydrophilicity and significantly depressed signal background. The as-developed fluorimetric platform, containing a MOF-coated microwells array, can enable the detection of ammonia in blood, with concentrations ranging linearly from 0.10 to 300 µM. More importantly, this plasma treatment-based fabrication route may hold promise for designing different wettable microwells arrays for the high-throughput detection of multiple targets in the fields of biomedical analysis and environmental monitoring.


Assuntos
Amônia/sangue , Fluorometria , Estruturas Metalorgânicas/química , Polímeros/química , Compostos de Estanho/química , Humanos , Estruturas Metalorgânicas/síntese química , Estrutura Molecular , Molhabilidade
11.
Anim Sci J ; 92(1): e13556, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33973682

RESUMO

The effect of alfalfa saponins (AS) supplementation on the meat quality especially the color for growing lamb was investigated. Fifty Hu male lambs with body weights (BW, 19.21 ± 0.45 kg) were divided into five groups and supplemented AS with 0, 500, 1,000, 2,000, and 4,000 mg/kg of dietary dry matter intake. After 90 days, all lambs were slaughtered. The longissimus thoracis muscle in lamb displayed significant changes in the content of intramuscular fat, especially n-3 polyunsaturated fatty acids, and drip loss within AS treatment (p < .05) between control and treatments groups. Redness (a*) significantly improved in both 0-day and 7-day storage with the AS supplementation coupled with the percentage of met-myoglobin reduction (p < .05). The redness (a*) change may result from improved met-myoglobin reducing activity, antioxidant enzymes, lactate dehydrogenase, and succinate dehydrogenase (p < .05) by AS supplementation in muscle. These enzymes may help to protect mitochondria function and reduce met-myoglobin, which bring a bright and red meat color.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Cor , Dieta/veterinária , Suplementos Nutricionais , Qualidade dos Alimentos , Carne , Medicago sativa/química , Músculo Esquelético/metabolismo , Mioglobina/metabolismo , Saponinas/administração & dosagem , Ovinos/crescimento & desenvolvimento , Ovinos/metabolismo , Tecido Adiposo/metabolismo , Animais , Ácidos Graxos Ômega-3/metabolismo , Armazenamento de Alimentos/métodos , Masculino , Carne/análise , Saponinas/isolamento & purificação , Fatores de Tempo
13.
Microorganisms ; 9(2)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33670077

RESUMO

A two-component system GtrS-GltR is required for glucose transport activity in P. aeruginosa and plays a key role during P. aeruginosa-host interactions. However, the mechanism of action of GtrS-GltR has not been definitively established. Here, we show that gltB, which encodes a periplasmic glucose binding protein, is essential for the glucose-induced activation of GtrS-GltR in P. aeruginosa. We determined that GltB is capable of binding to membrane regulatory proteins including GtrS, the sensor kinase of the GtrS-GltR TCS. We observed that alanine substitution of glucose-binding residues abolishes the ability of GltB to promote the activation of GtrS-GltR. Importantly, like the gtrS deletion mutant, gltB deletion mutant showed attenuated virulence in both Drosophila melanogaster and mouse models of infection. In addition, using CHIP-seq experiments, we showed that the promoter of gltB is the major in vivo target of GltR. Collectively, these data suggest that periplasmic binding protein GltB and GtrS-GltR TCS form a complex regulatory circuit that regulates the virulence of P. aeruginosa in response to glucose.

14.
Antioxidants (Basel) ; 10(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33573002

RESUMO

This study was designed to investigate the impact of dietary lycopene (antioxidant extracted from tomato) supplementation on postmortem antioxidant capacity, drip loss and protein expression profiles of lamb meat during storage. Thirty male Hu lambs were randomly divided into three treatment groups and housed in individual pens and received 0, 200 or 400 mg·kg-1 lycopene in their diet, respectively. All lambs were slaughtered after 3 months of fattening, and the longissimus thoracis (LT) muscle was collected for analyses. The results indicated that drip loss of LT muscle increased with storage days (P < 0.05). After storage for 7 days, significantly lower drip loss of meat was found in fed the lycopene-supplemented diet (P < 0.05). Dietary lycopene supplementation increased the activity of antioxidant enzymes (total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT)) (P < 0.05) and decreased the thiobarbituric acid reactive substance (TBARS) and carbonyl contents (P < 0.05). During the storage period (days 0, 5 and 7), a number of differentially abundant proteins (DAPs), including oxidases, metabolic enzymes, calcium channels and structural proteins, were identified based on iTRAQ data, with roles predominantly in carbon metabolism, oxidative phosphorylation, cardiac muscle contraction and proteasome pathways, and which contribute to decreased drip loss of lamb meat during storage. It can be concluded that dietary lycopene supplementation increased antioxidant capacity after slaughter, and the decreased drip loss during postmortem storage might occur by changing the expression of proteins related to enzyme activity and cellular structure in lamb muscle.

15.
Cell Death Dis ; 12(1): 87, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462188

RESUMO

Wilson's disease (WD) is an inherited disorder characterized by excessive accumulation of copper in the body, particularly in the liver and brain. In the central nervous system (CNS), extracellular copper accumulation triggers pathological microglial activation and subsequent neurotoxicity. Growing evidence suggests that levels of inflammatory cytokines are elevated in the brain of murine WD models. However, the mechanisms associated with copper deposition to neuroinflammation have not been completely elucidated. In this study, we investigated how the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to copper-mediated neuroinflammation in an animal model of WD. Elevated levels of interleukin-1ß, interleukin-18, interleukin-6, and tumor necrosis factor-α were observed in the sera of WD patients and toxic milk (TX) mice. The protein levels of inflammasome adaptor molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), cleaved caspase-1, and interleukin-1ß were upregulated in the brain regions of the TX mice. The NLRP3 inflammasome was activated in the TX mice brains. Furthermore, the activation of NLRP3 inflammasome was noted in primary microglia treated with CuCl2, accompanied by the increased levels of cleaved caspase-1, ASC, and interleukin-1ß. Blocking NLRP3 inflammasome activation with siNlrp3 or MCC950 reduced interleukin-1ß and interleukin-18 production, thereby effectively mitigating cognitive decline, locomotor behavior impairment, and neurodegeneration in TX mice. Overall, our study demonstrates the contribution of copper overload-mediated activation of NLRP3 inflammasome to progressive neuropathology in the CNS of a murine model of WD. Therefore, blockade of the NLRP3 inflammasome activation could be a potential therapeutic strategy for WD.


Assuntos
Cobre/metabolismo , Degeneração Hepatolenticular/metabolismo , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Animais , Cobre/toxicidade , Modelos Animais de Doenças , Feminino , Furanos/farmacologia , Técnicas de Silenciamento de Genes , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/patologia , Indenos/farmacologia , Inflamassomos/metabolismo , Interleucinas/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C3H , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfonamidas/farmacologia
16.
Angew Chem Int Ed Engl ; 60(1): 24-40, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592283

RESUMO

ß-Lactam antibiotics are generally perceived as one of the greatest inventions of the 20th century, and these small molecular compounds have saved millions of lives. However, upon clinical application of antibiotics, the ß-lactamase secreted by pathogenic bacteria can lead to the gradual development of drug resistance. ß-Lactamase is a hydrolase that can efficiently hydrolyze and destroy ß-lactam antibiotics. It develops and spreads rapidly in pathogens, and the drug-resistant bacteria pose a severe threat to human health and development. As a result, detecting and inhibiting the activities of ß-lactamase are of great value for the rational use of antibiotics and the treatment of infectious diseases. At present, many specific detection methods and inhibitors of ß-lactamase have been developed and applied in clinical practice. In this Minireview, we describe the resistance mechanism of bacteria producing ß-lactamase and further summarize the fluorogenic probes, inhibitors of ß-lactamase, and their applications in the treatment of infectious diseases. It may be valuable to design fluorogenic probes with improved selectivity, sensitivity, and effectiveness to further identify the inhibitors for ß-lactamases and eventually overcome bacterial resistance.


Assuntos
Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Corantes Fluorescentes/uso terapêutico , Resistência beta-Lactâmica/efeitos dos fármacos , Inibidores de beta-Lactamases/uso terapêutico , Humanos , Inibidores de beta-Lactamases/farmacologia
17.
Sci Signal ; 13(656)2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144518

RESUMO

Genetic mutations are a primary driving force behind the adaptive evolution of bacterial pathogens. Multiple clinical isolates of Pseudomonas aeruginosa, an important human pathogen, have naturally evolved one or more missense mutations in bfmS, which encodes the sensor histidine kinase of the BfmRS two-component system (TCS). A mutant BfmS protein containing both the L181P and E376Q substitutions increased the phosphorylation and thus the transcriptional regulatory activity of its cognate downstream response regulator, BfmR. This reduced acute virulence and enhanced biofilm formation, both of which are phenotypic changes associated with a chronic infection state. The increased phosphorylation of BfmR was due, at least in part, to the cross-phosphorylation of BfmR by GtrS, a noncognate sensor kinase. Other spontaneous missense mutations in bfmS, such as A42E/G347D, T242R, and R393H, also caused a similar remodeling of the BfmRS TCS in P. aeruginosa This study highlights the plasticity of TCSs mediated by spontaneous mutations and suggests that mutation-induced activation of BfmRS may contribute to host adaptation by P. aeruginosa during chronic infections.


Assuntos
Proteínas de Bactérias/metabolismo , Histidina Quinase/metabolismo , Mutação de Sentido Incorreto , Pseudomonas aeruginosa/enzimologia , Substituição de Aminoácidos , Proteínas de Bactérias/genética , Histidina Quinase/genética , Humanos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação
18.
Cureus ; 12(9): e10423, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-33062538

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic, there has been a global shortage of personal protective equipment (PPE). In this setting, cloth masks may play an important role in limiting disease transmission; however, current literature on the use of cloth masks remains inconclusive. This review aims to integrate current studies and guidelines to determine the efficacy and use of cloth masks in healthcare settings and/or the community. Evidence-based suggestions on the most effective use of cloth masks during a pandemic are presented. Embase, MEDLINE, and Google Scholar were searched on March 31, 2020, and updated on April 6, 2020. Studies reporting on the efficacy, usability, and accessibility of cloth masks were included. Additionally, a search of guidelines and recommendations on cloth mask usage was conducted through published material by international and national public health agencies. Nine articles were included in this review after full-text screening. The clinical efficacy of a face mask is determined by the filtration efficacy of the material, fit of the mask, and compliance to wearing the mask. Household fabrics such as cotton T-shirts and towels have some filtration efficacy and therefore potential for droplet retention and protection against virus-containing particles. However, the percentage of penetration in cloth masks is higher than surgical masks or N95 respirators. Cloth masks have limited inward protection in healthcare settings where viral exposure is high but may be beneficial for outward protection in low-risk settings and use by the general public where no other alternatives to medical masks are available.

20.
Ann Palliat Med ; 9(5): 2872-2885, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32787367

RESUMO

BACKGROUND: Gandou decoction (GDD) has been widely used in the treatment of Wilson disease (WD) for decades. It is optimized from the Dahuanghuanglianxiexin decoction, Yinchenhao decoction, and Huanglianjiedu decoction. It was first reported in the Treatise on Febrile and Miscellaneous Diseases and A Handbook of Prescriptions for Emergencies published in the Eastern Han Dynasty and the Eastern Jin Dynasty respectively. Hepatic injury is one of the most severe complications of WD. The current study aimed to explore the hepatic-protection effects of GDD and its exact therapeutic target, with a particular focus on the expression of oxidative stress and the Wnt/ß-catenin pathway. METHODS: Hepatic injury was induced in a copper-loaded rat model using the intragastric administration of copper(II) sulfate pentahydrate (CuSO4·5H2O). The water extract of GDD (0.4 g/kg/d) was administered twice a day for 4 weeks. Copper content and alanine aminotransferase (ALT) level, structural observation under the microscope, and immunohistochemical analysis of liver tissue were performed after the final administration. Moreover, the expression of ß-catenin, GSK3ß, Dishevelled-3, c-Myc, and p-GSK3ß of liver tissue were detected to explore the relationship between the hepatic protection of GDD and the Wnt/ ß-catenin signal pathway of GDD. We also stimulated the rat hepatic cell line BRL-3A with CuSO4·5H2O to establish a hepatic injury cytomodel. GDD serum at a concentration of 20% was administered into the model cell for 24 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry were performed to detect cell viability, mitochondrial membrane potential (MMP), and the expression of reactive oxygen species (ROS). Meanwhile, the expression of the Wnt/ß-catenin signal pathway-related proteins was evaluated. RESULTS: GDD reduced copper and ALT while inhibiting oxidative stress and the degeneration and necrosis of liver tissue and hepatocytes. Treatment with GDD improved cell viability and MMP while suppressing the ROS level. Furthermore, GDD rectified the expression of Wnt/ß-catenin signal pathway-related proteins in both livers of the copper-loaded and copper-stimulated BRL-3A cell lines. CONCLUSIONS: GDD had apparent therapeutic effects on the hepatic injury of copper-loaded rats and copper-stimulated BRL-3A cells. Its mechanism is related to its regulatory effect on the Wnt/ß-catenin pathway rectification and oxidative stress antagonism.


Assuntos
Degeneração Hepatolenticular , beta Catenina , Animais , China , Degeneração Hepatolenticular/tratamento farmacológico , Ratos , Via de Sinalização Wnt , beta Catenina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...