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1.
Analyst ; 149(7): 1971-1975, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38439614

RESUMO

Herein, we present toxicological assessments of carbon nanomaterials in HL-7702 cells, and it was found that reactive oxygen species (ROS) levels were elevated. Mass spectrometry results indicated that cysteine sulfhydryl of glutaredoxin-1 (GLRX1) was oxidized to sulfenic acids and sulfonic acids by excessive ROS, which broke the binding of GLRX1 to apoptosis signal-regulating kinase 1, causing the activation of the JNK/p38 signaling pathway and ultimately hepatocyte apoptosis. However, a lower level of ROS upregulated GLRX1 instead of sulfonation modification of its active sites. Highly expressed GLRX1 in turn enabled the removal of intracellular ROS, thereby exerting inconspicuous toxic effects on cells. Taken together, these findings emphasized that CNM-induced hepatotoxicity is attributable to oxidative modifications of GLRX1 arising from redox imbalance.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Glutarredoxinas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Glutarredoxinas/farmacologia , Oxirredução , Apoptose , Estresse Oxidativo
2.
Cancer Lett ; 588: 216746, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38387756

RESUMO

Helicobacter pylori (H. pylori) infection is considered to be an important factor in gastric cancer (GC). Long noncoding RNA (lncRNA) and m6A modification are involved in the occurrence and development of GC, but the role of lncRNA m6A modification in the development of GC mediated by H. pylori is still unclear. Here, we found that H. pylori infection downregulated the expression of lnc-PLCB1 through METTL14-mediated m6A modification and IRF2-mediated transcriptional regulation. Overexpression of lnc-PLCB1 inhibited the proliferation and migration of GC cells, while downregulation of lnc-PLCB1 promoted the proliferation and migration ability of GC cells. In addition, clinical analysis showed that lnc-PLCB1 is lower in GC tissues than in normal tissues. Further study found that lnc-PLCB1 reduced the protein stability of its binding protein DEAD-box helicase 21 (DDX21) and then downregulated the expression of CCND1 and Slug, thereby playing tumour suppressing role in the occurrence and development of GC. In conclusion, the METTL14/lnc-PLCB1/DDX21 axis plays an important role in H. pylori-mediated GC, and lnc-PLCB1 can be used as a new target for GC treatment.


Assuntos
Adenina , Infecções por Helicobacter , Helicobacter pylori , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Helicobacter pylori/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologia , Regulação para Baixo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Proliferação de Células , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Fosfolipase C beta/genética , Fosfolipase C beta/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo
3.
Sci Robot ; 9(87): eadh1978, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381838

RESUMO

Micro/nanorobotic swarms consisting of numerous tiny building blocks show great potential in biomedical applications because of their collective active delivery ability, enhanced imaging contrast, and environment-adaptive capability. However, in vivo real-time imaging and tracking of micro/nanorobotic swarms remain a challenge, considering the limited imaging size and spatial-temporal resolution of current imaging modalities. Here, we propose a strategy that enables real-time tracking and navigation of a microswarm in stagnant and flowing blood environments by using laser speckle contrast imaging (LSCI), featuring full-field imaging, high temporal-spatial resolution, and noninvasiveness. The change in dynamic convection induced by the microswarm can be quantitatively investigated by analyzing the perfusion unit (PU) distribution, offering an alternative approach to investigate the swarm behavior and its interaction with various blood environments. Both the microswarm and surrounding environment were monitored and imaged by LSCI in real time, and the images were further analyzed for simultaneous swarm tracking and navigation in the complex vascular system. Moreover, our strategy realized real-time tracking and delivery of a microswarm in vivo, showing promising potential for LSCI-guided active delivery of microswarm in the vascular system.


Assuntos
Imagem de Contraste de Manchas a Laser , Robótica , Fluxometria por Laser-Doppler/métodos , Fluxo Sanguíneo Regional
4.
Plant Physiol Biochem ; 206: 108289, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38154294

RESUMO

Mulberry is a traditional economic tree with various values in sericulture, ecology, food industry and medicine. Expansins (EXPs) are known as cell wall expansion related proteins and have been characterized to involve in plant development and responses to diverse stresses. In present study, twenty EXP and expansin-like (EXL) genes were identified in mulberry. RNA-seq results indicated that three EXP and EXL genes showed up-regulated expression level under sclerotiniose pathogen infection in three independent RNA-seq datasets. The most significant upregulated EXPA11 was selected as key EXP involving in response to sclerotiniose pathogen infection in mulberry. Furthermore, a comprehensive functional analysis was performed to reveal subcellular location, tissue expression profile of MaEXPA11 in mulberry. Down-regulation of MaEXPA11 using virus induced gene silence (VIGS) was performed to explore the function of MaEXPA11 in Morus alba. Results showed that MaEXPA11 can positively regulate mulberry resistance to Ciboria shiraiana infection and negatively regulate mulberry resistance to cold or drought stress.


Assuntos
Morus , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Morus/genética , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas
5.
Sci Adv ; 9(50): eadj0883, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100592

RESUMO

The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design-based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Sistemas de Liberação de Medicamentos , Animais , Coelhos , Sistemas de Liberação de Medicamentos/métodos , Impressão Tridimensional
6.
J Fungi (Basel) ; 9(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38132757

RESUMO

Lignin degradation is important for enhancing the digestibility and improving the nutritive quality of ruminant feeds. White rot fungi are well known for their bioconversion of lignocellulosic biomass. The objective of this paper was to evaluate whether Lentinus sajor-caju, Pleurotus ostreatus, Phyllotopsis rhodophylla, Pleurotus djamor, Pleurotus eryngii, and Pleurotus citrinopileatus treatments altered the chemical compositions of highland barley straw constituents and enhanced their nutritional value as a ruminant feed. All white rot fungi significantly increased the relative crude protein (CP), ethyl ether extract (EE), starch, soluble protein (SP), and non-protein nitrogen (NPN) contents but decreased the ash, neutral detergent fiber (NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), and acid detergent insoluble protein (ADFIP) contents. In addition, L. sajor-caju treatment increased (p < 0.001) the levels of PA, PB2, PB3, CA, CB1, CB2, and CNSC, but reduced (p < 0.001) the PC and CC in the solid-state fermentation of highland barley straw. Maximum ligninlysis (50.19%) was optimally produced in the presence of 1.53% glucose and 2.29% urea at 22.72 ℃. The in vitro dry matter digestibility and total volatile fatty acid concentrations of fermented highland barley straw, as well as the fermentability, were optimized and improved with L. sajor-caju, which degraded the lignocellulose and improved the nutritional value of highland barley straw as a ruminant feed.

7.
Nat Commun ; 14(1): 7539, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985765

RESUMO

The rapid diagnosis of respiratory virus infection through breath and blow remains challenging. Here we develop a wireless, battery-free, multifunctional pathogenic infection diagnosis system (PIDS) for diagnosing SARS-CoV-2 infection and symptom severity by blow and breath within 110 s and 350 s, respectively. The accuracies reach to 100% and 92% for evaluating the infection and symptom severity of 42 participants, respectively. PIDS realizes simultaneous gaseous sample collection, biomarker identification, abnormal physical signs recording and machine learning analysis. We transform PIDS into other miniaturized wearable or portable electronic platforms that may widen the diagnostic modes at home, outdoors and public places. Collectively, we demonstrate a general-purpose technology for rapidly diagnosing respiratory pathogenic infection by breath and blow, alleviating the technical bottleneck of saliva and nasopharyngeal secretions. PIDS may serve as a complementary diagnostic tool for other point-of-care techniques and guide the symptomatic treatment of viral infections.


Assuntos
Líquidos Corporais , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Manejo de Espécimes , Saliva
8.
Curr Med Imaging ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37936439

RESUMO

BACKGROUND: In late December 2019, Wuhan, the capital of Hubei Province, China, became the center of an outbreak of pneumonia caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). INTRODUCTION: The radiological changes in the lungs of critical people with coronavirus disease 2019 (COVID-19) pneumonia at different times have not been fully characterized. We aim to describe the computed tomography findings of patients with critical COVID-19 pneumonia at different disease stages. METHODS: Clinical and laboratory features of critical patients were assessed. CT scans were assigned to groups 1, 2, 3, or 4 based on the interval from symptom onset (within 2 weeks; ≥ 2-4 weeks; ≥ 4-6 weeks; or ≥ 6 weeks, respectively). Imaging features were analyzed and compared across the four groups. Total CT scores, corresponding periods of laboratory findings, and glucocorticoid dosages during the imaging intervals were longitudinally observed in five patients with complete data. RESULTS: All 11 critical patients (median age: 60 years [42-69]) underwent a total of 40 CT examinations, and the acquisition times ranged from 1-59 days after symptom onset. Median total CT scores were 18 (9-25.25); 44.5 (42.88-47.62); 43.75 (38.62-49.38); and 42 (32.25-53.25) in groups 1, 2, 3, and 4, respectively. The observed lesions were mainly bilateral (37 [92.5%]). The median values of involved lung segments were 10.5 (4.5-13.5); 17 (16-18.5); 18 (18-19.5); and 18 (18-19) in groups 1-4, respectively. The predominant patterns of observed abnormalities were ground-glass opacities (GGO) (9 [90%]); GGO with reticulation and mixed patterns (3 [37.5%] for both); GGO with consolidation (3 [30%]); and GGO with reticulation (8 [66.7%]) in groups 1-4, respectively. Patients developed fibrotic manifestations at later stages. CONCLUSION: Critical patients with COVID-19 infection generally presented with temporally changing abnormal CT features from focal unilateral to diffuse bilateral GGO and consolidation that progressed to or coexisted with reticulation in the long term after symptom onset. Low-dose glucocorticoids may be effective in patients with interstitial changes on CT findings.

9.
Adv Sci (Weinh) ; 10(28): e2300822, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37552813

RESUMO

The rising incidence of health-endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX-A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer-specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX-A and the resulting therapeutic effects. The drug-loaded tips of the layer-specific gastric paralysis microneedles (LGP-MN) rapidly release and achieve uniform distribution of BTX-A within the designated gastric wall layers. In an obesity rat model, the LGP-MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06-fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach-derived glucagon-like peptide-1 due to the muscularis-targeting LGP-MN treatment is an important contributor to its unique glucose tolerance-improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX-A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP-MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes.

10.
Cell Signal ; 109: 110771, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37329997

RESUMO

Disulfiram (DSF) has proven to be a promising anti-tumor drug in preclinical studies. However, its anti-cancer mechanism has not yet been elucidated. As an activator in tumor metastasis, N-myc downstream regulated gene-1 (NDRG1) is involved in multiple oncogenic signaling pathways and is upregulated by cell differentiation signals in various cancer cell lines. DSF treatment results in a significant reduction in NDRG1, while down-regulated NDRG1 has a pronounced effect on invading cancer cells, as shown in our previous work. Here, in vitro and in vivo experiments confirm that DSF contributes to regulating tumor growth, EMT, and the migration and invasion of cervical cancer. Furthermore, our results show DSF binds to the ATP-binding pocket in the N-terminal domain of HSP90A, thereby affecting the expression of its client protein NDRG1. To our knowledge, this is the first report of DSF binding to HSP90A. In conclusion, this study sheds light on the molecular mechanism by which DSF inhibits tumor growth and metastasis through the HSP90A/NDRG1/ß-catenin pathway in cervical cancer cells. These findings provide novel insights into the mechanism underlying DSF function in cancer cells.


Assuntos
Dissulfiram , Neoplasias do Colo do Útero , Feminino , Humanos , Dissulfiram/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Proteínas de Ciclo Celular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Regulação Neoplásica da Expressão Gênica
11.
BMC Pregnancy Childbirth ; 23(1): 358, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198553

RESUMO

BACKGROUND: Antenatal depression (AD) is a major depressive disorder during pregnancy, which may lead to devastating sequelae for the expectant mothers and infants. This study aimed to investigate the prevalence, to analyze trajectory model based on EPDS score, and to explore the influence factors of AD among pregnant women in Chengdu, China. METHODS: Participants from four maternity hospitals in Chengdu, China were recruited when they had their first pregnancy medical check-up during March 2019 to May 2020. All participants were required to fill in Edinburgh Postnatal Depression Scale Chinese version (EPDS) once during three trimesters and provided information about their health status, social-demographic etc. The trajectory model, chi-square test and multivariate binary logistic regression were used to analyze all collected data. RESULTS: A total of 4560 pregnant women were recruited, while 1051 women completed the study. The prevalence of depression symptoms during the first, second and third trimesters were 32.92% (346/1051), 19.79% (208/1051) and 20.46% (215/1051) respectively. According to the results of the latent growth mixture modeling, the trajectory model of three categories based on EPDS score were identified in this study: low-risk group (38.2%, 401/1051), medium-risk group (54.8%, 576/1051) and high-risk group (7%, 74/1051). Good marital relationship (P = 0.007, OR = 0.33, 95% CI 0.147 ~ 0.74), good relationship with parents-in-law (P = 0.011, OR = 0.561, 95% CI 0.36 ~ 0.874), planned pregnancy (P = 0.018, OR = 0.681, 95% CI 0.496 ~ 0.936) were the protective factors while lower education level (P = 0.036, OR = 1.355, 95% CI 1.02 ~ 1.799), fear about dystocia (P = 0.0, OR = 1.729, 95% CI 1.31 ~ 2.283), recent major negative life events (P = 0.033, OR = 2.147, 95% CI 1.065 ~ 4.329) were the risk factors of medium-risk group. Good marital relationship (P = 0.005, OR = 0.2, 95% CI 0.065 ~ 0.615), good relationship with parents-in-law (P = 0.003, OR = 0.319, 95% CI 0.15 ~ 0.679) were also protective factors of high-risk group, but the risk factors for high-risk group were medical history (P = 0.046, OR = 1.836, 95% CI 1.011 ~ 3.334), pregnancy complications (P = 0.022, OR = 2.015, 95% CI 1.109 ~ 3.662), worry about dystocia (P = 0.003, OR = 2.365, 95% CI 1.347 ~ 4.153), recent major negative life events (P = 0.011, OR = 3.661, 95% CI 1.341 ~ 9.993). No protective or risk factors were identified for low-risk group. CONCLUSION: Even the incidence and levels of depression in the first trimester of pregnancy were the highest, the probability of pregnancy women get depression during gestation period were higher than other population. Therefore, it's important to monitor the psychological status of pregnant women during the whole pregnancy, especially in the first trimester. The study suggested a good partner relationship and good relations with parents-in-law both protected pregnant women from depression and promoted the well-being of mothers and children.


Assuntos
Depressão Pós-Parto , Transtorno Depressivo Maior , Complicações na Gravidez , Criança , Feminino , Gravidez , Humanos , Depressão/epidemiologia , Depressão/diagnóstico , Prevalência , Estudos Prospectivos , Mães/psicologia , Fatores de Risco , China/epidemiologia , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/psicologia
12.
Polymers (Basel) ; 15(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37177294

RESUMO

Multi-scale "rigid-soft" material coating has been an effective strategy for enhancing the interfacial shear strength (IFSS) of carbon fibers (CFs), which is one of the key themes in composite research. In this study, a soft material, chitosan (CS), and a rigid material, carbon nanotubes (CNTs), were sequentially grafted onto the CFs surface by a two-step amination reaction. The construction of the "rigid-soft" structure significantly increased the roughness and activity of the CFs surface, which improved the mechanical interlocking and chemical bonding between the CFs and resin. The interfacial shear strength (IFSS) of the CS- and CNT-modified CFs composites increased by 186.9% to 123.65 MPa compared to the desized fibers. In addition, the tensile strength of the modified CFs was also enhanced by 26.79% after coating with CS and CNTs. This strategy of establishing a "rigid-soft" gradient modulus interfacial layer with simple and non-destructive operation provides a valuable reference for obtaining high-performance CFs composites.

13.
Sci Adv ; 9(10): eade8622, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36888700

RESUMO

Electrical stimulation is a promising method to modulate gastrointestinal disorders. However, conventional stimulators need invasive implantation and removal surgeries associated with risks of infection and secondary injuries. Here, we report a battery-free and deformable electronic esophageal stent for wireless stimulation of the lower esophageal sphincter in a noninvasive fashion. The stent consists of an elastic receiver antenna infilled with liquid metal (eutectic gallium-indium), a superelastic nitinol stent skeleton, and a stretchable pulse generator that jointly enables 150% axial elongation and 50% radial compression for transoral delivery through the narrow esophagus. The compliant stent adaptive to the dynamic environment of the esophagus can wirelessly harvest energy through deep tissue. Continuous electrical stimulations delivered by the stent in vivo using pig models significantly increase the pressure of the lower esophageal sphincter. The electronic stent provides a noninvasive platform for bioelectronic therapies in the gastrointestinal tract without the need for open surgery.


Assuntos
Esfíncter Esofágico Inferior , Trato Gastrointestinal , Animais , Suínos , Stents , Pressão , Estimulação Elétrica
14.
Artigo em Inglês | MEDLINE | ID: mdl-36078812

RESUMO

Due to the ecotoxicity of 17ß-estradiol (E2), residual E2 in the environment poses potential risks to human and animal health and ecosystems. Biodegradation is considered one of the most effective strategies to remove E2 from the environment. Here, a novel, efficient E2-degrading bacterial strain Microbacterium resistens MZT7 was isolated from activated sludge and characterized. The genome of strain MZT7 contained 4,011,347 bp nucleotides with 71.26% G + C content and 3785 coding genes. There was 86.7% transformation efficiency of 10 mg/L E2 by strain MZT7 after incubation for 5 d at optimal temperature (30 °C) and pH (7.0). This strain was highly tolerant to ranges in pH (5.0-11.0), temperature (20-40 °C), and salinity (2-8%). Adding sources of carbon (glucose, maltose, sucrose, or lactose) or nitrogen sources (urea, peptone, or beef extract) promoted the degradation of E2 by strain MZT7. However, when yeast extract was added as a nitrogen source, the degradation efficiency of E2 was inhibited. Metabolites were analyzed by LC-MS and three metabolic pathways of E2 degradation were proposed. Further, the intermediates dehydroepiandrosterone and androsta-1,4-diene-3,17-dione were detected, as well as identification of kshB and fadD3 genes by KEGG, confirming one E2 degradation pathway. This study provided some insights into E2 biodegradation.


Assuntos
Ecossistema , Estradiol , Animais , Bactérias/metabolismo , Biodegradação Ambiental , Bovinos , Estradiol/metabolismo , Humanos , Microbacterium , Nitrogênio
15.
Front Med (Lausanne) ; 9: 955992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911395

RESUMO

This case report describes a 58-year-old, never-smoking housewife with chief complaints of progressively worsening cough, dyspnea, and intermittent fever, who was initially misdiagnosed with community-acquired pneumonia (CAP). However, her pulse oximetry oxygen saturation continued to decline, and eventually, she underwent an endotracheal intubation. Fortunately, transbronchial cryobiopsy (TBCB) assisted by extracorporeal membrane oxygenation (ECMO) was performed in the most critical situation, and it revealed an organizing pneumonia (OP) pattern. OP describes a histological pattern of acute or subacute pulmonary damage, which may be idiopathic or associated with a known or unknown underlying disease. A definitive diagnosis of OP usually obtained from pathology, and surgical lung biopsy with large lung tissue is recommended. However, since the surgical lung biopsy was not convenient for this patient after mechanical ventilation, bedside TBCB supported by ECMO was selected. To our knowledge, we are the first to report the pathological diagnosis of ECMO assisted TBCB in acute respiratory failure. When oxygenation cannot be maintained after endotracheal intubation and surgical lung biopsy is not feasible, ECMO-supported TBCB may be a good choice to obtain lung tissue for histopathological diagnosis in patients with acute lung injury of unknown etiology.

16.
Chem Commun (Camb) ; 58(60): 8432-8435, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35796322

RESUMO

Dual emission almost covering the entire NIR-II region with the maximum full width at half maximum of 542 nm was achieved by doping small amounts of Pb ions into Ag2Se quantum dots, which to the best of our knowledge has not been realized for continuous tunable dual NIR emission in Ag-based QDs. The fabricated broadband NIR mini light-emitting diodes based on the Pb-doped Ag2Se QDs exhibit potential applications for highly sensitive and multispectral non-invasive imaging and NIR lighting.


Assuntos
Pontos Quânticos , Chumbo
17.
Appl Environ Microbiol ; 88(13): e0043722, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35736228

RESUMO

The amino sugar N-acetyl-d-glucosamine (GlcNAc) is the key constituent of cell wall components and plays an important role in pathogenesis in a wide range of fungi. However, catabolism of GlcNAc has not been studied in basidiomycete fungi. In this study, we identified and characterized a gene cluster essential for GlcNAc utilization in Cryptococcus deneoformans, an environmental human fungal pathogen. The C. deneoformans genome contains a GlcNAc transporter (Ngt1), a GlcNAc kinase (Hxk3), a GlcNAc-6-phosphate deacetylase (Dac1), and a glucosamine-6-phosphate deaminase (Nag1). Their expression levels were highly induced in cultures containing GlcNAc as the sole carbon source, and the corresponding mutants showed severe growth defects in the presence of GlcNAc. Functional and biochemical analyses revealed that HXK3 encodes a novel GlcNAc kinase. Site-directed mutations of conserved residues of Hxk3 indicated that ATP binding and GlcNAc binding are essential for GlcNAc kinase activities. Taken together, the results from this study provide crucial insights into basidiomycete GlcNAc catabolism. IMPORTANCEN-Acetylglucosamine (GlcNAc) is recognized as not only the building block of chitin but also an important signaling molecule in fungi. The catabolic pathway of GlcNAc also plays an important role in vital biological processes in fungi. However, the utilization pathway of GlcNAc in the phylum Basidiomycota, which contains more than 41,000 species, remains unknown. Cryptococcus deneoformans is a representative basidiomycetous pathogen that causes life-threatening meningitis. In this study, we characterized a gene cluster essential for GlcNAc utilization in C. deneoformans and identified a novel GlcNAc kinase. The results of this study provide important insights into basidiomycete GlcNAc catabolism and offer a starting point for revealing its role in pathogenesis.


Assuntos
Candida albicans , Cryptococcus , Acetilglucosamina/metabolismo , Parede Celular/metabolismo , Quitina/metabolismo , Humanos
18.
J Am Chem Soc ; 144(21): 9443-9450, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35603745

RESUMO

Efficient transfection of therapeutic agents and timely potency testing are two key factors hindering the development of cellular therapy. Here we present a cellular-nanoporation and exosome assessment device, a quantitative platform for nanochannel-based cell electroporation and exosome-based in situ RNA expression analysis. In its application to transfection of anti-miRNAs and/or chemotherapeutics into cells, we have systematically described the differences in RNA expression in secreted exosomes and assessed cellular therapies in real time.


Assuntos
Exossomos , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Transfecção
19.
Molecules ; 27(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35630816

RESUMO

Mulberry (Morus spp., Moraceae) is an important economic crop plant and is rich in flavonoids and anthocyanidins in ripe fruits. Anthocyanins are glycosides of anthocyanidins. Flavanone 3-hydroxylase (F3H) catalyzes the conversion of naringenin into dihydroflavonols and is responsible for the biosynthesis of flavonols and anthocyanidins. In this study, MazsF3H was cloned and characterized from Morus atropurpurea var. Zhongshen 1. Conserved motif analysis based on alignment and phylogenetic analysis indicated that MazsF3H belonged to 2-oxoglutarate-dependent dioxygenase and MazsF3H clustered with F3Hs from other plants. MazsF3H was located in both nucleus and cytosol. MazsF3H was expressed in stems, leaves, stigmas and ovaries, except buds. F3H expression levels showed a positive and close relationship with anthocyanin content during the anthocyanin-rich fruit ripening process, while it showed a negative correlation with anthocyanin content in LvShenZi, whose fruits are white and would not experience anthocyanin accumulation during fruit ripening. Significantly different F3H expression levels were also found in different mulberry varieties that have quite different anthocyanin contents in ripe fruits. Overexpression MazsF3H in tobacco showed unexpected results, including decreased anthocyanin content. Down-regulation of F3H expression levels resulted in co-expression of the genes involved in anthocyanin biosynthesis and a significant decrease in anthocyanin content, but the change in total flavonoid content was subtle. Our results indicated that F3H may play quite different roles in different varieties that have quite different fruit colors. In addition, possible complex regulation of flavonoid biosynthesis should be further explored in some of the featured plant species.


Assuntos
Antocianinas , Morus , Antocianinas/metabolismo , Flavonoides/metabolismo , Frutas/genética , Frutas/metabolismo , Oxigenases de Função Mista , Morus/genética , Morus/metabolismo , Filogenia
20.
Front Public Health ; 10: 870065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480580

RESUMO

Aim: Syndecan-1 (SDC-1) has been shown to have a high predictive value for sepsis development, though uncertainty around these results exists. The aim of this meta-analysis was to assess the prognostic ability of SDC-1 in predicting sepsis-related complications and mortality. Methods: We searched PubMed, EMBASE, Cochrane Library, and Google Scholar databases from January 01, 1990, to March 17, 2021, to identify eligible studies. The search terms used were "SDC-1," "sepsis," "severe sepsis," and "septic shock," and a meta-analysis was performed using the RevMan 5.4 software. Results: Eleven studies with a total of 2,318 enrolled patients were included. SDC-1 concentrations were significantly higher in the composite poor outcome group [standardized mean difference (SMD) = 0.55; 95% CI: 0.38-0.72; P < 0.001] as well as in deceased patients (SMD = 0.53; 95% CI: 0.40-0.67; P < 0.001), patients with septic shock (SMD = 0.81; 95% CI: 0.36-1.25; P < 0.001), and patients with acute kidney injury (SMD = 0.48; 95% CI: 0.33-0.62; P < 0.001). Statistical significance was also found in the subgroup analysis when stratified by different sepsis diagnostic criteria. Conclusion: Baseline SDC-1 levels may be a useful predictor of sepsis-related complications and mortality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246344, PROSPERO, identifier: CRD42021246344.


Assuntos
Sepse , Choque Séptico , Humanos , Prognóstico , Sepse/complicações , Sindecana-1
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