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1.
J Hazard Mater ; 441: 129826, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36084456

RESUMO

Metastasis includes tumor invasion and migration and underlies over 90% of cancer mortality. The metastatic effects of environmental carcinogens raised serious health concerns. However, the underlying mechanisms remained poorly studied. In the present study, an in vivo RasV12/lgl-/- model of the fruitfly, Drosophila melanogaster, with an 8-day exposure was employed to explore the metastatic effects of 3,3',4,4',5-pentachlorobiphenyl (PCB126), perfluorooctanoic acid (PFOA) and cadmium chloride (CdCl2). At 1.0 mg/L, PCB126, PFOA, and CdCl2 significantly increased tumor invasion rates by 1.32-, 1.33-, and 1.29-fold of the control, respectively. They also decreased the larval body weight and locomotion behavior. Moreover, they commonly disturbed the expression levels of target genes in MAPK and UPR pathways, and their metastatic effects were significantly abolished by the addition of p38 inhibitor (SB203580), JNK inhibitor (SP600125) and IRE1 inhibitor (KIRA6). Notably, the addition of the IRE inhibitor significantly influenced sna/E-cad pathway which is essential in both p38 and JNK regulations. The results demonstrated an essential role of sna/E-cad in connecting the effects of carcinogens on UPR and MAPK regulations and the resultant metastasis.


Assuntos
Carcinógenos Ambientais , Neoplasias , Animais , Cloreto de Cádmio , Caprilatos , Drosophila , Drosophila melanogaster , Fluorcarbonetos , Proteínas Serina-Treonina Quinases , Transdução de Sinais
2.
Food Chem ; 402: 134197, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36182779

RESUMO

Carbendazim (CBZ) is beneficial to fruit and vegetable cultivation, but its residue will cause fruit and vegetable juice pollution. In this work, an electrochemical sensor based on carbon nanohorns@reduced graphene oxide coated by gold platinum core-shell nanoparticles (Au@Pt/CNHs@RGO/GCE) was prepared for CBZ detection. The results showed that the assembly of CNHs and RGO assisted by ultrasound improved the electron transfer ability and electrochemical active surface area of CNHs@RGO. Moreover, the coating of Au@Pt nanoparticles further enhanced the sensitivity of the sensor. With the synergistic effect of the three materials, the sensor had a wider linear range (0.05 µmol/L-50 µmol/L), a lower limit of detection (1.64 nmol/L), and satisfactory recovery rates (90.60 % ∼ 97.60 %, carrot juice; 94.00-114.43 %, orange juice). Additionally, the sensor presented good anti-interference and repeatability. This work provides a simple, rapid, economical, sensitive, and accurate sensor for CBZ quantification in fruit and vegetable juice.


Assuntos
Grafite , Nanopartículas Metálicas , Ouro/química , Platina/química , Carbono/química , Sucos de Frutas e Vegetais , Frutas , Nanopartículas Metálicas/química , Grafite/química , Técnicas Eletroquímicas , Eletrodos , Limite de Detecção
3.
Artigo em Inglês | MEDLINE | ID: mdl-36342667

RESUMO

Ginsenoside Rg1 is one of the major ginsenosides found in roots of Panax ginseng and Panax notoginseng. Ginsenoside Rg1 is known to possess various biological activities including immunity enhancement activity. However, it is not clear whether the regulation of immune function by Rg1 is related to the intestinal microbiota. In the present study, the immuno-modulatory and gut microbiota-reshaping effects of ginsenoside Rg1 were evaluated. Ginsenoside Rg1 acts as an immune-enhancing agent to increase spleen index and the number of T, B and dendritic cells in dexamethasone (Dex)-treated mice. Ginsenoside Rg1 also increased the production of sIgA and regulated the expression of interleukin 2 (IL-2), IL-4, IL-10 and IFN-γ. Meanwhile, Rg1 administration regulated the structure of intestinal microbiota. The relative abundance of mouse intestinal microbial groups, such as Alistipes, Ruminococcaceae, Lachnospiraceae, and Roseburia were increased by Rg1 administration, whereas a decrease in the potential pathogens like Helicobacteraceae, Dubosiella, Mycoplasma, Alloprevotella, Allobaculum was observed. Moreover, Rg1 metabolites of Lachnospiraceae bacterium enhanced the proliferation of CD4+ T cells and T regulatory (Treg) cells. Ginsenoside Rg1 improved the inflammatory condition of the colonic tissue and repaired the destructed mucosal barrier. This study suggested that Rg1 strengthens immunity with regulating the homeostasis of intestinal microbiota in mice.

4.
Org Biomol Chem ; 20(45): 8849-8854, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36326261

RESUMO

An enantioselective addition of 5-amino-isoxazoles with ß,γ-alkynyl-α-ketimino esters catalyzed by a chiral phosphoric acid has been developed. This procedure allowed the formation of quaternary α-isoxazole-α-alkynyl amino acid derivatives with high yields (up to 99%) and good to excellent enantioselectivities (up to 97%), and the corresponding products enabled many further elaborations. The control experiment revealed that the hydrogen-bonding interaction of 5-amino-isoxazole with the chiral phosphoric acid played a vital role in the enantioselectivity, and the transition state of the reaction was proposed.


Assuntos
Aminoácidos , Isoxazóis , Estereoisomerismo , Estrutura Molecular , Catálise , Aminoácidos/química
5.
Front Bioeng Biotechnol ; 10: 972361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406214

RESUMO

Since more and more large-scale farms appear in China and changes in fecal sewage source disposal, the production of high-concentration solid manure waste is also increasing, and its conversion and utilization are gaining attention. This study investigated the effect of heat pre-treatment (HPT) on the thermophilic anaerobic digestion (AD) of high-solid manure (HSM). Pig manure (PM) feed with a total solids of 13% was used for the HPT and subsequent anaerobic digestion (AD) test. The HPT was carried out at 60°C, 80°C, and 100°C, respectively, for 15 min after the heating reached the set temperature. The results show that HPT led to PM feed COD solubilization, observing a maximum increase of 24.57% after pretreated at 100°C, and the treated PM feed under this condition received the maximum methane production potential of 264.64 mL·g-1 VS in batch AD test, which was 28.76% higher than that of the untreated group. Another semi-continuous AD test explored the maximum volume biogas production rate (VBPR). It involves two organic loading rates (OLR) of 13.4 and 17.8 g VSadded·L-1·d-1. The continuous test exhibited that all the HPT groups could produce biogas normally when the OLR increased to the high level, while the digester fed with untreated PM showed failure. The maximum VBPR of 4.71 L L-1·d-1 was observed from PM feed after pre-treated at 100°C and running at the high OLR. This reveals that thermal treatment can weaken the impact of a larger volume of feed on the AD system. Energy balance analysis demonstrates that it is necessary to use a heat exchanger to reuse energy in the HPT process to reduce the amount of energy input. In this case, the energy input to energy output (E i /E o ) ranged from 0.34 to 0.55, which was much less than one, suggesting that biogas increment due to heat treatment can reasonably cover the energy consumption of the pre-treatment itself. Thus combining HPT and high-load anaerobic digestion of PM was suitable.

6.
PLoS Genet ; 18(10): e1010136, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36279281

RESUMO

Accurate chromosome segregation requires a cohesin-mediated physical attachment between chromosomes that are to be segregated apart, and a bipolar spindle with microtubule plus ends emanating from exactly two poles toward the paired chromosomes. We asked whether the striking bipolar structure of C. elegans meiotic chromosomes is required for bipolarity of acentriolar female meiotic spindles by time-lapse imaging of mutants that lack cohesion between chromosomes. Both a spo-11 rec-8 coh-4 coh-3 quadruple mutant and a spo-11 rec-8 double mutant entered M phase with separated sister chromatids lacking any cohesion. However, the quadruple mutant formed an apolar spindle whereas the double mutant formed a bipolar spindle that segregated chromatids into two roughly equal masses. Residual non-cohesive COH-3/4-dependent cohesin on separated sister chromatids of the double mutant was sufficient to recruit haspin-dependent Aurora B kinase, which mediated bipolar spindle assembly in the apparent absence of chromosomal bipolarity. We hypothesized that cohesin-dependent Aurora B might activate or inhibit spindle assembly factors in a manner that would affect their localization on chromosomes and found that the chromosomal localization patterns of KLP-7 and CLS-2 correlated with Aurora B loading on chromosomes. These results demonstrate that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion.


Assuntos
Caenorhabditis elegans , Proteínas Cromossômicas não Histona , Animais , Feminino , Caenorhabditis elegans/genética , Proteínas Cromossômicas não Histona/genética , Proteínas de Ciclo Celular/genética , Meiose/genética , Cromátides/genética , Segregação de Cromossomos/genética , Fuso Acromático/genética
7.
Eur J Nucl Med Mol Imaging ; 49(13): 4427-4439, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35925443

RESUMO

PURPOSE: Accurate identification of nodal status enables adequate neck irradiation for nasopharyngeal carcinoma (NPC). However, most conventional techniques are unable to pick up occult metastases, leading to underestimation of tumor extensions. Here we investigate the clinical significance of carbonic anhydrase IX (CAIX) in human NPC samples, and develop a CAIX-targeted imaging strategy to identify occult lymph node metastases (LNMs) and extranodal extension (ENE) in animal studies. METHODS: A total of 211 NPC samples are performed CAIX staining, and clinical outcomes are analyzed. The metastatic murine models are generated by foot pad injection of NPC cells, and a CAIX-targeted imaging agent (CAIX-800) is intravenously administered. We adopt fluorescence molecular tomography and ultrasonography (US)-guided spectroscopic photoacoustic (sPA) imaging to perform in vivo studies. Histological and immunohistochemical characterization are carried out via node-by-node analysis. RESULTS: For clinical samples, 90.1% (91/101) primary tumors, 73.3% (66/90) metastases, and 100% (20/20) local recurrences are CAIX positive. In metastases group, 84.7% (61/72) nodal metastases and 22.2% (4/18) organ metastases are CAIX positive. CAIX expression in primary tumors is significantly associated with NPC stage and prognosis. For animal studies, CAIX-800-based fluorescence imaging achieves 81.3% sensitivity and 93.8% specificity in detecting occult LNMs in vivo, with a minimum detectable diameter of 1.7 mm. Coupled with CAIX-800, US-guided sPA imaging could not only detect subcapsular deposits of metastatic cancer cells 2 weeks earlier than conventional techniques, but also successfully track pathological ENE. CONCLUSION: CAIX remarkably expresses in human NPCs and stratifies patient prognosis. In preclinical studies, CAIX-800-based imaging successfully identifies occult LNMs and tracks early stage of pathological ENE. This attractive method shows potential in clinic, allowing medical workers to longitudinally monitor nodal status and helping to reduce unnecessary nodal biopsy for patients with NPC. The schematic diagram for the study. CAIX, carbonic anhydrase IX; NPC, nasopharyngeal carcinoma; US, ultrasonography; sPA, spectroscopic photoacoustic.


Assuntos
Anidrases Carbônicas , Neoplasias Nasofaríngeas , Humanos , Camundongos , Animais , Anidrase Carbônica IX/metabolismo , Carcinoma Nasofaríngeo/diagnóstico por imagem , Anidrases Carbônicas/análise , Anidrases Carbônicas/metabolismo , Biomarcadores Tumorais/metabolismo , Prognóstico , Antígenos de Neoplasias/análise , Metástase Linfática , Neoplasias Nasofaríngeas/diagnóstico por imagem , Modelos Animais
8.
Acta Pharm Sin B ; 12(11): 4154-4164, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35968270

RESUMO

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro and PLpro with IC50 values of 1.73 ± 0.22 and 3.91 ± 0.19 µmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC50 of 11.83 ± 3.23 µmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

9.
Sci Total Environ ; 851(Pt 2): 158324, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36037905

RESUMO

Carbendazim (CBZ) can protect crops from pathogens, but it is also easy to cause pesticide residues, threatening human health. In our work, an electrochemical sensor based on nitrogen-doped carbon nanohorns (N-CNHs) and polyethyleneimine-modified carbon nanotubes (PEI-CNTs) was developed for the detection of CBZ content in water. The results showed that N-doping provided the CN bonds for CNHs and improved the electrochemical reaction performance of N-CNHs surface. With the participation of PEI, the surface of CNTs was positively charged and contained a large number of NH bonds, which not only promoted the electrostatic assembly of N-CNHs and PEI-CNTs but also was beneficial to further enriching CBZ. After further ultrasound-assisted assembly of N-CNHs and PEI-CNTs, the electron transfer capacity, electrochemical active surface area, and catalytic activity of N-CNHs/PEI-CNTs were significantly improved. The sensor performed a wider linear range (15 nmol/L ~ 70 µmol/L), low detection limit (4 nmol/L) and satisfactory recovery (87.33 % ~ 117.67 %) under the optimal conditions. In addition, the sensor had good anti-interference, reproducibility, and stability. Our work provided a new strategy for quantification of CBZ in environment.


Assuntos
Nanotubos de Carbono , Resíduos de Praguicidas , Humanos , Nanotubos de Carbono/química , Polietilenoimina/química , Técnicas Eletroquímicas/métodos , Nitrogênio/química , Água , Reprodutibilidade dos Testes
10.
Ann Intensive Care ; 12(1): 72, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35934730

RESUMO

BACKGROUND: The mortality of extensively drug-resistant Gram-negative (XDR GN) bacilli-induced ventilator-associated pneumonia (VAP) is extremely high. The purpose of this study was to compare the efficacy and safety of inhaled (IH) plus intravenous (IV) polymyxin B versus IV polymyxin B in XDR GN bacilli VAP patients. METHODS: A retrospective multi-center observational cohort study was performed at eight ICUs between January 1st 2018, and January 1st 2020 in China. Data from all patients treated with polymyxin B for a microbiologically confirmed VAP were analyzed. The primary endpoint was the clinical cure of VAP. The favorable clinical outcome, microbiological outcome, VAP-related mortality and all-cause mortality during hospitalization, and side effects related with polymyxin B were secondary endpoints. Favorable clinical outcome included clinical cure or clinical improvement. RESULTS: 151 patients and 46 patients were treated with IV polymyxin B and IH plus IV polymyxin B, respectively. XDR Klebsiella pneumoniae was the main isolated pathogen (n = 83, 42.1%). After matching on age (± 5 years), gender, septic shock, and Apache II score (± 4 points) when polymyxin B was started, 132 patients were included. 44 patients received simultaneous IH plus IV polymyxin B and 88 patients received IV polymyxin B. The rates of clinical cure (43.2% vs 27.3%, p = 0.066), bacterial eradication (36.4% vs 23.9%, p = 0.132) as well as VAP-related mortality (27.3% vs 34.1%, p = 0.428), all-cause mortality (34.1% vs 42.0%, p = 0.378) did not show any significant difference between the two groups. However, IH plus IV polymyxin B therapy was associated with improved favorable clinical outcome (77.3% vs 58.0%, p = 0.029). Patients in the different subgroups (admitted with medical etiology, infected with XDR K. pneumoniae, without bacteremia, with immunosuppressive status) were with odd ratios (ORs) in favor of the combined therapy. No patient required polymyxin B discontinuation due to adverse events. Additional use of IH polymyxin B (aOR 2.63, 95% CI 1.06, 6.66, p = 0.037) was an independent factor associated with favorable clinical outcome. CONCLUSIONS: The addition of low-dose IH polymyxin B to low-dose IV polymyxin B did not provide efficient clinical cure and bacterial eradication in VAP caused by XDR GN bacilli. Keypoints Additional use of IH polymyxin B was the sole independent risk factor of favorable clinical outcome. Patients in the different subgroups were with HRs substantially favoring additional use of IH polymyxin B. No patients required polymyxin B discontinuation due to adverse events.

11.
Cell Div ; 17(1): 4, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933447

RESUMO

BACKGROUND: Cell invasion is a crucial step of tumor metastasis, finding new regulators of which offers potential drug targets for cancer therapy. Aberrant GLYAT expression is associated with human cancers, yet its role in cancer remains unknown. This study aims to understand the function and mechanism of Drosophila GLYAT in cell invasion. RESULTS: We found that dGLYAT regulates Gadd45-mediated JNK pathway activation and cell invasion. Firstly, loss of dGLYAT suppressed scrib depletion- or Egr overexpression-induced JNK pathway activation and invasive cell migration. Secondary, mRNA-seq analysis identified Gadd45 as a potential transcriptional target of dGLYAT, as depletion of dGLYAT decreased Gadd45 mRNA level. Finally, Gadd45 knockdown suppressed scrib depletion-induced JNK pathway activation and cell invasion. CONCLUSIONS: These evidences reveal the role of dGLYAT and Gadd45 in JNK-dependent cell invasion, and provide insight for the roles of their human homologs in cancers.

12.
Front Pharmacol ; 13: 917827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784732

RESUMO

This study investigated the effects of berberine (BBR) on pancreatic cancer (PC) lung metastasis and explored the underlying mechanisms, using a BALB/C-nu/nu nude mouse model injected with PC cells (AsPC-1). Intragastric administration of BBR dose-dependently improves survival of mice intravenously injected with AsPC-1 cells, and reduces lung metastasis. Especially, BBR significantly reduces lung infiltration of circulating tumor cells (CTCs) 24 h after AsPC-1 cells injection. In vitro, tumor cells (TCs) trigger endothelial barrier disruption and promote trans-endothelial migration of CFSE-labeled TCs. BBR treatment effectively ameliorates TC-induced endothelial disruption, an effect that is diminished by inhibiting transforming growth factor-ß receptor 1 (TGFBR1). Blocking TGFBR1 blunts the anti-metastatic effect of BBR in vivo. Mechanistically, BBR binds to the intercellular portion of TGFBR1, suppresses its enzyme activities, and protects endothelial barrier disruption by TCs which express higher levels of TGF-ß1. Hence, BBR might be a promising drug for reducing PC lung metastasis in clinical practice.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35897391

RESUMO

Direct-absorption anaerobic reactors can maintain the fermentation process of microorganisms by utilizing solar absorption and scattering media in the biogas reactor to improve the slurry temperature. Direct-absorption heating alone can save the corresponding electric energy and ensure the normal fermentation process of the biogas slurry in the reactor, but there is still the problem of temperature fluctuation. In order to improve the stability of the fermentation process, it is proposed to optimize the design of this kind of reactor by adding paraffin phase change material. This article mainly studies the influence of paraffin phase change material added on the top and side of the reactor in the fermentation process and gives the corresponding design parameters for different climatic conditions, which lays a theoretical reference for the design process of this kind of reactor.


Assuntos
Biocombustíveis , Reatores Biológicos , Anaerobiose , Parafina , Temperatura
14.
Nanoscale Horiz ; 7(7): 779-789, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35703339

RESUMO

Nano-tumor interactions are fundamental for cancer nanotherapy, and the cross-talk of nanomedicines with the extracellular matrix (ECM) is increasingly considered essential. Here, we specifically investigate the nano-ECM interactivity using drug-free nanoparticulates (NPs) and highly metastatic cancer cells as models. We discover with surprise that NPs closely bind to specific types of ECM components, namely, retraction fibers (RFs) and migrasomes, which are located at the rear of tumor cells during their migration. This interaction is observed to alter cell morphology, limit cell motion range and change cell adhesion. Importantly, NPs are demonstrated to inhibit tumor cell removal in vitro, and their anti-metastasis potential is preliminarily confirmed in vivo. Mechanically, the NPs are found to coat and form a rigid shell on the surface of migrasomes and retraction fibers via interaction with lipid raft/caveolae substructures. In this way, NPs block the recognition, endocytosis and elimination of migrasomes by their surrounding tumor cells. Thereby, NPs interfere with the cell-ECM interaction and reduce the promotion effect of migrasomes on cell movement. Additionally, NPs trigger alteration of the expression of proteins related to cell-cell adhesion and cytoskeleton organization, which also restricts cell migration. In summary, all the findings here provide a potential target for anti-tumor metastasis nanomedicines.


Assuntos
Matriz Extracelular , Neoplasias , Cavéolas/patologia , Adesão Celular , Movimento Celular , Endocitose , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Humanos
15.
Bioresour Technol ; 359: 127471, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35710052

RESUMO

The unreasonable disposal of residue after anaerobic digestion seriously affects the stability of the ecosystem, and the preparation of adsorbent is an effective way to value-added utilization of the residue. In this study, a high adsorption capacity (209.65 mg/g) biochar-based adsorbent was prepared by hydrothermal carbonization and alkali modification using rice straw biogas residue. The lignocellulosic structure was destroyed after anaerobic digestion, forming porous biochar with larger specific surface area (2372.51 m2/g) and richer pore structure. Besides, the mercury ion complexed on the adsorbent surface in monovalent and divalent forms and possessed favorable selectivity in the presence of other examples of interference. The adsorption process is consistent with pseudo second-order kinetics and the Langmuir isotherm, indicating a predominance of chemisorption. This study provides a methodology for use of rice straw biogas residue and treatment of mercury containing wastewater, which offers a fresh direction for resource utilization of biogas residue.


Assuntos
Mercúrio , Nanoporos , Oryza , Poluentes Químicos da Água , Adsorção , Biocombustíveis , Carvão Vegetal/química , Digestão , Ecossistema , Cinética , Oryza/química , Água , Poluentes Químicos da Água/química
16.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(3): 336-341, 2022 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-35678448

RESUMO

OBJECTIVE: In order to grasp the quality status of the first-aid ventilator in pre-hospital and field environment in time, the quality control and detection items of invasive ventilator were optimized to form a rapid detection operation process of first-aid ventilator and ensure the safety of patient treatment. METHODS: Based on the quality control detection data of invasive ventilator in hospital in recent years, methods such as narrowing the range of qualified criteria and analyzing confidence interval were adopted to extract indicators prone to deviation and verify their correlation with similar indicators, so as to form an optimized rapid detection portfolio. RESULTS: Compared with the original quality control detection procedures, the detection indicators of the rapid detection procedures were reduced from 5 categories of 24 indicators to 3 categories of 7 indicators. The detection time was shortened by 56.1% and the coincidence rate of the detection results was 100% after the actual measurement and verification. CONCLUSIONS: Under the premise of ensuring the testing quality, the operating procedure for rapid detection of emergency ventilator can greatly reduce the detection time, and realize the rapid and high frequency quality control detection, so as to ensure the quality and safety of the equipment.


Assuntos
Serviços de Assistência Domiciliar , Ventiladores Mecânicos , Humanos , Controle de Qualidade
17.
Angew Chem Int Ed Engl ; 61(33): e202201266, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35761432

RESUMO

The interconversion of guanosine triphosphate (GTP) and guanosine diphosphate (GDP) is known to be integral to a wide variety of biological cellular activities, yet to date there are no analytical methods available to directly detect the ratio of intracellular GTP to GDP. Herein, we report GRISerHR, a genetically encoded fluorescent biosensor to monitor the GTP : GDP ratio in multiple cell types and in various organelles under metabolic perturbation. Additionally, we characterized the differential mitochondrial GTP : GDP ratios resulting from genetic modulation of two isoforms of a tricarboxylic acid (TCA) cycle enzyme (succinyl-CoA synthetase; SCS-ATP and SCS-GTP) and of a phosphoenolpyruvate (PEP) cycle enzyme (PEPCK-M). Thus, our GRISerHR sensor achieves spatiotemporally precise detection of dynamic changes in the endogenous GTP : GDP ratio in living cells and can help deepen our understanding about the energy metabolic contributions of guanosine nucleotides in biology.


Assuntos
Técnicas Biossensoriais , Succinato-CoA Ligases , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Mitocôndrias/metabolismo , Succinato-CoA Ligases/metabolismo
18.
Biochem Biophys Res Commun ; 614: 125-131, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35580541

RESUMO

Timely and accurate diagnosis of acute ischemic stroke (AIS) and simultaneous functional imaging of cerebral oxygen saturation (sO2) are essential to improve the survival rate of stroke patients but remains challenging. Herein, we developed a pH-responsive manganese (Mn)-based nanoplatform as a magnetic resonance/photoacoustic (MR/PA) dual-modal contrast agent for AIS diagnosis. The Mn-based nanoplatform was prepared via a simple and green biomimetic method using bovine serum albumin (BSA) as a scaffold for fabrication of MnCO3 NPs as the T1 MR contrast agent and accommodation of indocyanine green (ICG) as the PA probe. The obtained MnCO3@BSA-ICG NPs were biocompatible and exhibited a pH-responsive longitudinal relaxation rate and a concentration-dependent PA signal. In vivo MR/PA dual-modal imaging demonstrated that MnCO3@BSA-ICG NPs quickly and efficiently led to the MR/PA contrast enhancements in the infarcted area while not in the normal region, allowing a timely and accurate diagnosis of AIS. Moreover, PA imaging could directly monitor the sO2 level, enabling a functional imaging of AIS. Therefore, MnCO3@BSA-ICG NPs could be applied as a potential MR/PA contrast agent for timely and functional imaging of AIS.


Assuntos
AVC Isquêmico , Nanopartículas , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Meios de Contraste , Humanos , Verde de Indocianina , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Fototerapia/métodos , Soroalbumina Bovina
19.
Eur J Nucl Med Mol Imaging ; 49(8): 2723-2734, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35590110

RESUMO

PURPOSE: A sensitive and specific imaging method to detect metastatic cancer cells in lymph nodes to detect the early-stage breast cancer is still a challenge. The purpose of this study was to investigate a novel breast cancer-targeting and tumour microenvironment ATP-responsive superparamagnetic iron oxide nanoparticles (SPIOs) imaging probe (abbreviated as SPIOs@A-T) that was developed to detect lymph node metastasis through fluorescence molecular imaging (FMI) and magnetic particle imaging (MPI). METHODS: The conjugation of the targeted peptide CREKA and SPIOs was via linker sulfo-SMCC, while the dsDNA-Cy5.5 was modified on SPIOs through the conjugation between maleimide group in sulfo-SMCC and sulfydryl group in dsDNA-Cy5.5. SPIOs@A-T was characterised for its imaging properties, targeting ability and toxicity in vitro. Mice with metastatic lymph node (MLN) of breast cancer were established to evaluate the FMI and MPI imaging strategy in vivo. Healthy mice with normal lymph node (NLN) were used as control group. Histological examination and biosafety evaluation were performed for further assessment. RESULTS: After injection with SPIOs@A-T, the obvious high fluorescent intensity and MPI signal were observed in MLN group than those in NLN group. FMI can specifically light up MLN using an ATP-responsive fluorescence design. On the other hand, MPI could complement the limitation of imaging depth from FMI and could detect MLN more sensitively. Besides, the biosafety evaluation results showed SPIOs@A-T had no detectable biological toxicity. CONCLUSION: SPIOs@A-T imaging probe in combination with FMI and MPI can provide a promising novel method for the precise detection of MLN in vivo.


Assuntos
Neoplasias da Mama , Nanopartículas de Magnetita , Segunda Neoplasia Primária , Trifosfato de Adenosina , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Meios de Contraste , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Melanoma , Camundongos , Neoplasias Cutâneas , Microambiente Tumoral
20.
Front Immunol ; 13: 844427, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401499

RESUMO

Most of the membrane molecules involved in immune response are glycosylated. N-glycans linked to asparagine (Asn) of immune molecules contribute to the protein conformation, surface expression, stability, and antigenicity. Core fucosylation catalyzed by core fucosyltransferase (FUT8) is the most common post-translational modification. Core fucosylation is essential for evoking a proper immune response, which this review aims to communicate. First, FUT8 deficiency suppressed the interaction between µHC and λ5 during pre-BCR assembly is given. Second, we described the effects of core fucosylation in B cell signal transduction via BCR. Third, we investigated the role of core fucosylation in the interaction between helper T (TH) cells and B cells. Finally, we showed the role of FUT8 on the biological function of IgG. In this review, we discussed recent insights into the sites where core fucosylation is critical for humoral immune responses.


Assuntos
Fucose , Imunidade Humoral , Fucose/metabolismo , Fucosiltransferases , Glicosilação , Imunoglobulina G
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