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1.
Nat Chem ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658798

RESUMO

Natural gap junctions are a type of channel protein responsible for intercellular signalling and mass communication. However, the scope of applications for these proteins is limited as they cannot be prepared at a large scale and are unable to spontaneously insert into cell membranes in vitro. The construction of artificial gap junctions may provide an alternative strategy for preparing analogues of the natural proteins and bottom-up building blocks necessary for the synthesis of artificial cells. Here we show the construction of artificial gap junction channels from unimolecular tubular molecules consisting of alternately arranged positively and negatively charged pillar[5]arene motifs. These molecules feature a hydrophobic-hydrophilic-hydrophobic triblock structure that allows them to efficiently insert into two adjacent plasma membranes and stretch across the gap between the two membranes to form gap junctions. Similar to natural gap junction channels, the synthetic channels could mediate intercellular signal coupling and reactive oxygen species transmission, leading to cellular activity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38551423

RESUMO

Objective: This study aims to investigate the impact of ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement on gastrointestinal burden in patients with severe acute pancreatitis. Methods: A cohort of 116 patients with severe acute pancreatitis admitted to the hospital from August 2021 to July 2023 were included. They were randomly divided into the control group (58 cases, nasal intestinal tube placement using ultrasound-guided combined water injection) and the observation group (58 cases, nasal intestinal tube placement using ultrasound-guided combined with water and air mixed injection). The incubation time, volume of water injected during the incubation, nasal intestinal tube visualization rate, and success rate of one-time incubation were recorded for both groups. Gastrointestinal mucosal barrier function, Nutritional index level including intestinal fatty acid-binding protein (I-FABP), D-lactate and nutritional index levels including hemoglobin (Hb), serum albumin (ALB), retinol-binding protein (RBP) were compared between the two groups before tube placement and at 7 days after incubation. Complications in both groups were also recorded. Results: The incubation time in the observation group was shorter, and the volume of water injected during the incubation was lower than in the control group. The nasal intestinal tube visualization rate and success rate of one-time incubation were higher in the observation group (P < .05). At 7 days after incubation, the levels of I-FABP and D-lactate were lower in the observation group than in the control group (P < .05). At 7 days after incubation, The levels of I-FABP and D-lactate in the observation group were lower than those in the control group, Hb and RBP levels were higher in the observation group than in the control group (P < .05), while there was no significant difference in ALB levels between the two groups (P > .05). The incidence of complications was lower in the observation group than in the control group (P < .05). Conclusion: Ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement in patients with severe acute pancreatitis can shorten the incubation time, reduce the volume of water injected during the incubation, improve the nasal intestinal tube visualization rate and success rate of one-time incubation, enhance gastrointestinal mucosal barrier function and nutritional index in patients, and reduce the incidence of complications.

3.
ACS Appl Mater Interfaces ; 16(9): 11997-12006, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38394677

RESUMO

The low concentration of water-based lubricants and the high chemical inertness of the additives involved are often regarded as basic norms in the design of liquid lubricants. Herein, a novel liquid superlubricant of an aqueous solution containing a relatively high concentration of salt, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), is reported for the first time, and the superlubricity stability and load-bearing capacity of the optimized system (MgO0.10/LiTFSI10) are effectively strengthened by the addition of only trace (0.10 wt %) water-chemically active MgO additives. It demonstrates higher applicable loads, lower COF (∼0.004), and stability relative to the base solution. Only a trace amount of MgO additive is needed for the superlubricity, which makes up for the cost and environmental deficiencies of LiTFSI10. The weak interaction region between free water and the outer-layer water of Li+ hydration shells becomes a possible ultralow shear resistance sliding interface; the Mg(OH)2 layer, generated by the reaction of MgO with water, further creates additional weakly interacting interfaces, leading to the formation of an asymmetric contact between the clusters/particles within the hydrodynamic film by moderating the competition between interfacial water and free water, thus achieving high load-bearing macroscopic superlubricity. This study deepens the contribution of electrolyte concentration to ionic hydration and superlubricity due to the low shear slip layer formed by interfacial water competition with water-activated solid additives, providing new insights into the next generation of high load-bearing water-based liquid superlubricity systems.

4.
Nanomicro Lett ; 16(1): 97, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285078

RESUMO

Engineering transition metal compounds (TMCs) catalysts with excellent adsorption-catalytic ability has been one of the most effective strategies to accelerate the redox kinetics of sulfur cathodes. Herein, this review focuses on engineering TMCs catalysts by cation doping/anion doping/dual doping, bimetallic/bi-anionic TMCs, and TMCs-based heterostructure composites. It is obvious that introducing cations/anions to TMCs or constructing heterostructure can boost adsorption-catalytic capacity by regulating the electronic structure including energy band, d/p-band center, electron filling, and valence state. Moreover, the electronic structure of doped/dual-ionic TMCs are adjusted by inducing ions with different electronegativity, electron filling, and ion radius, resulting in electron redistribution, bonds reconstruction, induced vacancies due to the electronic interaction and changed crystal structure such as lattice spacing and lattice distortion. Different from the aforementioned two strategies, heterostructures are constructed by two types of TMCs with different Fermi energy levels, which causes built-in electric field and electrons transfer through the interface, and induces electron redistribution and arranged local atoms to regulate the electronic structure. Additionally, the lacking studies of the three strategies to comprehensively regulate electronic structure for improving catalytic performance are pointed out. It is believed that this review can guide the design of advanced TMCs catalysts for boosting redox of lithium sulfur batteries.

5.
ACS Omega ; 8(13): 11813-11823, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37033859

RESUMO

Fly ash from coal-fired power plants can enter chemical absorbents along with flue gas. Silica and metal oxides are the main components of fly ash. To explore the effect of the metal oxides on absorbents, we analyzed the integrated CO2 absorption-desorption process using N-methyldiethanolamine (MDEA) as the standard and an amine absorbent after adding different metal oxides. The effects of each metal oxide on CO2 capture by the MDEA solution, including CO2 reaction heat, absorption rate, cyclic loading, and carbonation rate, were assessed. It was found that supplementation with appropriate calcium oxide and magnesium oxide proportions accelerates the CO2 absorption rate and shortens the saturation time of the MDEA solution by 9%-17%. Magnesium oxide and calcium oxide were precipitated as carbonates during absorption. The CO2 reaction heat of the MDEA solution increased by 95% after adding magnesium oxide, thereby significantly increasing the energy consumption of the desorption process. On the basis of the experimental studies, the increase in CO2 absorption rate by MDEA after adding MgO and CaO may be mediated through two different mechanisms.

6.
J Phys Chem Lett ; 14(2): 453-459, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36622949

RESUMO

A high load-carrying capacity is the key to the practicality of liquid superlubricity, but it is difficult to achieve high load and low friction simultaneously by relying solely on a liquid film. Herein, a choline chloride-based ionic liquid analogue (ILA) macroscale superlubricant is first reported by tuning down strong hydrogen bonding in the ILA via introducing 2-10 wt % water, with a high load of 160 MPa and a low coefficient of friction of 0.006-0.008. In situ Raman reveals that competitive exchange between external water and crystalline water induces weak H-bond-dominated incomplete hydration, conferring a low-shear interface and considerable load-carrying capacity inside the lubricant. It is a hydrodynamic lubrication film rather than a tribochemical/physical adsorption film, allowing it to be applied to friction pairs of various materials. This study unveils the principle of water mediation of high-viscosity ILAs and also provides new insights into the design of practical ILA-based superlubrication materials with high load-carrying capacity.

7.
Trials ; 23(1): 294, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413886

RESUMO

BACKGROUND: Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT. METHODS: This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety. DISCUSSION: This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 .


Assuntos
Sepse , Choque Séptico , Adolescente , Adulto , Antibacterianos , Estado Terminal , Humanos , Meropeném/efeitos adversos , Meropeném/farmacocinética , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/diagnóstico , Sepse/tratamento farmacológico , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico
8.
J Am Chem Soc ; 143(30): 11332-11336, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34270229

RESUMO

We developed a voltage-sensitive artificial transmembrane channel by mimicking the dipolar structure of natural alamethicin channel. The artificial channel featured a zwitterionic structure and could undergo voltage-driven flipping in the lipid bilayers. Importantly, this flipping of the channel could lead to their directional alignment in the bilayers and rectifying behavior for ion transport.


Assuntos
Canais Iônicos/química , Bicamadas Lipídicas/química , Condutividade Elétrica , Transporte de Íons , Estrutura Molecular , Prata/química , Compostos de Prata/química
9.
Infect Genet Evol ; 91: 104804, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33684569

RESUMO

OBJECTIVES: To explore if SOCS1 is regulated by plasma HDL and its subcomponents HDL2b and HDL3 to affect inflammatory reaction then to influence the severity degree and prognosis of sepsis. METHODS: One hundred sepsis patients in ICU and 85 normal control persons from October 2018 to October 2019 in our hospital were enrolled. Adult male C57BL/6 mice were used to establish sepsis model by CLP method. HDL, CRP, and WBC count of human were measured using an auto-analyzer. Plasma HDL, IL-1ß, and TNF-α proteins levels of mice were measured with ELISA. Microfluidic chip was used for plasma HDL2b and HDL3 detections. SOCS1 in liver and spleen of mice were measured by qRT-PCR. The relationship between plasma HDL//HDL2b and inflammatory indices/SOCS1 in liver/spleen was analyzed with spearman correlation coefficient method. The sepsis patients/mice were divided into non-survival and survival groups. The sepsis patients were divided into severe and mild sepsis patients based on the SOFA score or divided into high and low score groups according to the APACHE II score. The sepsis mice were divided into high and low score group based on the modified sepsis severity score criterion. RESULTS: Plasma HDL and HDL2b levels were significantly declined (P < 0.01), while HDL3 was normal in both sepsis patients and mice (P > 0.05). Plasma HDL and HDL2b were negatively associated with the serum CRP concentration and positively correlated with the prognosis and severity in sepsis patients (P < 0.05). Moreover, the downregulated plasma HDL but not HDL2b was negatively related to increased SOCS1 mRNA levels in liver and spleen of mice, which were positively connected with TNF-α and IL-1ß protein levels (P < 0.05). CONCLUSIONS: Plasma HDL is downregulated in sepsis, which may facilitate inflammatory reaction then activate the SOCS1 signaling to regulate the severity and affect prognosis of sepsis. The decline of plasma HDL2b content could aggravate the severity and poor prognosis of sepsis through facilitating inflammatory reaction. The plasma HDL3 is not involved in sepsis. The more and further explorations may be needed.


Assuntos
Inflamação/metabolismo , Lipoproteínas HDL/sangue , Sepse/imunologia , Transdução de Sinais/imunologia , Proteína 1 Supressora da Sinalização de Citocina/genética , Adulto , Idoso , China , Feminino , Humanos , Lipoproteínas HDL2/sangue , Lipoproteínas HDL3/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo , Sepse/metabolismo , Índice de Gravidade de Doença , Baço/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/metabolismo
10.
Chem Commun (Camb) ; 57(9): 1097-1100, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33443269

RESUMO

A series of glycoside-peptide conjugates were prepared by engineering at the N-terminus of the natural peptide gramicidin A. The conjugate containing galactose moiety formed a unimolecular transmembrane channel and mediated ion transport to induce apoptosis of cancer cells. More importantly, it exhibited liver cancer cell-targeting behavior due to the galactose-asialoglycoprotein receptor recognition.


Assuntos
Apoptose/efeitos dos fármacos , Gramicidina/química , Gramicidina/farmacologia , Transporte de Íons/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Antineoplásicos , Linhagem Celular Tumoral , Humanos , Canais Iônicos , Transporte de Íons/fisiologia , Bicamadas Lipídicas
11.
Appl Opt ; 59(32): 10149-10159, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33175792

RESUMO

Bonding has been used to repair carbon fiber-reinforced polymer (CFRP) materials. However, research has shown that resin residue on the surface of CFRP can cause adhesion problems. Therefore, a reliable surface cleaning procedure is necessary to remove the resin residue before bonding. In this paper, the surface resin was removed by laser cleaning, while the surface properties of CFRP were improved. A pulsed laser cleaning experiment was designed to study the chemical activity and bonding strength of CFRP treated by laser with different laser power and scanning speed. The results showed that as the contact angle of the material surface decreased, chemical activity and adhesive properties were improved. The surface pretreated with laser power of 16 W (scanning speed of 1500 mm/s) had no resin residue and the best adhesive properties; the bonding strength was 1.6 times higher than that of the untreated surface, and the failure mode was dominated by a cohesive damage mode.

12.
Discov Med ; 29(157): 129-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002409

RESUMO

Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.


Assuntos
Infecções Bacterianas/microbiologia , Ácidos Nucleicos Livres/sangue , DNA Bacteriano/sangue , Sepse/microbiologia , Adulto , Idoso , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Betacoronavirus , COVID-19 , Teste para COVID-19 , Ácidos Nucleicos Livres/análise , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Técnicas de Cultura , DNA Bacteriano/análise , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pandemias , Pneumonia Viral , Reação em Cadeia da Polimerase , SARS-CoV-2 , Sepse/complicações , Sepse/diagnóstico , Análise de Sequência de DNA
13.
J Pharm Biomed Anal ; 164: 231-240, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30391812

RESUMO

Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.


Assuntos
Gastrite Atrófica/prevenção & controle , Gastrodia/química , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/imunologia , Gastrite Atrófica/metabolismo , Humanos , Espectroscopia de Ressonância Magnética/instrumentação , Masculino , Metabolômica/instrumentação , Extratos Vegetais/farmacologia , Purinas/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Toxicol Res (Camb) ; 7(5): 834-847, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30310661

RESUMO

Owing to the promising applications of C-dots in biomedical engineering, concerns about their safety have drawn increasing attention recently. In this study, mice were intraperitoneally injected at different C-dot concentrations (0, 6.0, 12.0 and 24.0 mg kg-1) once every 2 days for 30 days. A 1H NMR-based metabolic approach supplemented with biochemical analysis and histopathology was used for the first time to explore the toxicity of C-dots in vivo. Histopathological inspection revealed that C-dots did not induce any obvious impairment in tissues. Biochemical assays showed no significant alterations of most measured biochemical parameters in tissues and serum, except for a slight reduction of the albumin level in serum as well as AChE activity in the liver and kidneys. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles supplemented with correlation network analysis and SUS-plots disclosed that C-dots not only triggered the immune system but also disturbed the function of cell membranes as well as the normal liver clearance, indicating that the 1H NMR based metabolomics approach provided deep insights into the toxicity of C-dots in vivo and gained an advantage over traditional toxicological means, and should be helpful for the understanding of its toxic mechanism.

15.
Toxicol Lett ; 295: 256-269, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29936297

RESUMO

Isoniazid (INH) is a well-known therapeutic and preventive agent against tuberculosis. However, high rates of side effects with various symptoms concerning hepatotoxicity and neurotoxicity have been reported, hindering its wide and safe application in clinic. In this investigation, rats were intoxicated with INH by gavage at doses of 200 and 400 mg/kg for 7 consecutive days to develop a rat model of acute INH-induced toxicity, which was investigated by a 1H NMR-based metabolomics complemented with clinical assays, histopathological inspection and western blotting. INH decreased the weights of dosed rats and induced seizure and hepatic steatosis dose-dependently. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of the NMR profiles of rat livers, brains and serum revealed that INH dose-dependently induced oxidative stress, disorders of excitatory and inhibitory amino acid neurotransmitters, and disturbances of energy metabolism and osmotic balance, which could help clarify the mechanisms of INH-induced hepatotoxicity and neurotoxicity. This integrated metabolomics approach showcased its ability to characterize the global metabolic status of organism, providing a powerful and feasible tool to probe drug induced toxicity or side effects.


Assuntos
Antituberculosos/toxicidade , Encéfalo/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Isoniazida/toxicidade , Fígado/efeitos dos fármacos , Metabolômica/métodos , Síndromes Neurotóxicas/etiologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Espectroscopia de Prótons por Ressonância Magnética , Convulsões/induzido quimicamente , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/sangue , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Análise Discriminante , Metabolismo Energético/efeitos dos fármacos , Estudos de Viabilidade , Análise dos Mínimos Quadrados , Fígado/metabolismo , Fígado/patologia , Masculino , Síndromes Neurotóxicas/sangue , Síndromes Neurotóxicas/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Reconhecimento Automatizado de Padrão , Ratos Sprague-Dawley , Convulsões/sangue , Convulsões/fisiopatologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-29770473

RESUMO

Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed. Cell apoptosis was also analyzed by flow cytometry, while western blotting was performed to examine the activation of EGFR and its downstream kinases in H1650 cells after Icotinib and radiation treatment. Furthermore, a xenograft animal model was established to evaluate the radiosensitivity of Icotinib in vivo and to confirm its mechanism. Our results demonstrate that pretreatment with Icotinib reduced clonogenic survival after radiation, inhibited EGFR activation, and increased radiation-induced apoptosis in H1650 cells. The phosphorylation of protein kinase B (AKT), extracellular regulated protein kinase 1/2 (ERK1/2), and EGFR was inhibited after Icotinib and radiation combination treatment in vitro and in vivo compared with individual treatments. Combination treatment also affected the expression of the DNA repair protein H2A histone family member X (γ-H2AX). In conclusion, our results reveal that Icotinib enhances radiosensitivity in lung cancers in vitro and in vivo and the mechanism of this may involve blocking the EGFR-AKT and MAPK-ERK pathways and limiting DNA repair.

17.
Metab Brain Dis ; 32(4): 1295-1309, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28584907

RESUMO

Datura metel L. (D. metel) is one well-known folk medical herb with wide application and also the most abused plants all over the world, mainly for spiritual or religious purpose, over-dosing of which often produces poisonous effects. In this study, mice were orally administered with the extract of D. metel once a day at doses for 10 mg/kg and 40 mg/kg for consecutive 4 days, 1H NMR based metabolomics approach aided with histopathological inspection and biochemical assays were used for the first time to study the psychoactive and toxic effects of D. metel. Histopathological inspection revealed obvious hypertrophy of hepatocytes, karyolysis and karyorrhexis in livers as well as distinct nerve cell edema, chromatolysis and lower nuclear density in brains. The increased tissue level of methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD), decreased tissue level of glutathione (GSH) along with increased serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) suggested brain and liver injury induced by D. metel. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles supplemented with correlation network analysis revealed significant altered metabolites and related pathway that contributed to oxidative stress, energy metabolism disturbances, neurotransmitter imbalance and amino acid metabolism disorders.


Assuntos
Encéfalo/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Datura metel/toxicidade , Fígado/efeitos dos fármacos , Extratos Vegetais/toxicidade , Animais , Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glutationa/metabolismo , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Metabolômica , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
18.
Front Microbiol ; 8: 769, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28515715

RESUMO

This study reported the efficacy of the metabolites of Plectosphaerella cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against Pseudomonas aeruginosa quorum sensing (QS) and QS-regulated biofilms. The minimum inhibitory concentration (MIC) of the ethyl acetate (EtOAc) extract from P. cucumerina against P. aeruginosa PAO1 was 1.25 mg mL-1. At sub-MIC concentrations, P. cucumerina extract (0.25-1 mg mL-1) not only inhibited biofilm formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without affecting its growth. Fluorescence and scanning electron microscope (SEM) showed architectural disruption of the biofilms when treated with P. cucumerina metabolites. Further investigation demonstrated that metabolites in P. cucumerina attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with experimentally standard samples suggested that patulin and emodin might act as the principal components possessing anti-biofilm and antivirulence activities. This is the first report of (1) the isolation of P. cucumerina from the phyllosphere of O. violaceus and (2) anti-biofilm, antivirulence, and biofilm disruption activities of this fungus. Thus, this study provides fascinating new pathways for screening antipathogenic agents.

19.
Aquat Toxicol ; 188: 159-169, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28528318

RESUMO

Glyphosate is an efficient herbicide widely used worldwide. However, its toxicity to non-targeted organisms has not been fully elucidated. In this study, the toxicity of glyphosate-based herbicide was evaluated on goldfish (Carassius auratus) after long-term exposure. Tissues of brains, kidneys and livers were collected and submitted to NMR-based metabolomics analysis and histopathological inspection. Plasma was collected and the blood biochemical indexes of AST, ALT, BUN, CRE, LDH, SOD, GSH-Px, GR and MDA were measured. Long-term glyphosate exposure caused disorders of blood biochemical indexes and renal tissue injury in goldfish. Metabolomics analysis combined with correlation network analysis uncovered significant perturbations in oxidative stress, energy metabolism, amino acids metabolism and nucleosides metabolism in glyphosate dosed fish, which provide new clues to the toxicity of glyphosate. This integrated metabolomics approach showed its applicability in discovering the toxic mechanisms of pesticides, which provided new strategy for the assessment of the environmental risk of herbicides to non-target organisms.


Assuntos
Glicina/análogos & derivados , Carpa Dourada/metabolismo , Herbicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glicina/toxicidade , Rim/metabolismo , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Estresse Oxidativo/efeitos dos fármacos , Glifosato
20.
J Proteome Res ; 16(2): 824-830, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28094526

RESUMO

Quorum sensing (QS) is a process of bacterial communication that has been a novel target for drug discovery. Pyocyanin quantification assay confirmed that resveratrol was an effective quorum sensing inhibitor (QSI) against Pseudomonas aeruginosa PAO1. In this study, the global metabolite changes of P. aeruginosa PAO1 exposed to QSI resveratrol were investigated by 1H NMR spectroscopy. A total of 40 metabolites containing amino acids, organic acid, organic amine, and energy storage compounds were identified. The changed metabolic profile indicated that resveratrol influenced pathways including oxidative stress, protein synthesis, and energy metabolism. Oxidative stress could upregulate the expression of genes related to QS in P. aeruginosa. It suggested that resveratrol could inhibit the QS systems in P. aeruginosa PAO1 by relieving oxidative stress due to its antioxidant activity. On the other hand, resveratrol could attenuate the pathogenicity of P. aeruginosa PAO1 by disturbing the TCA cycle so that anaerobic respiration could suppress the virulence because anaerobiosis could induce the loss of cytotoxicity regulated by QS in P. aeruginosa. These findings deepened our comprehending of the metabolic responses of P. aeruginosa PAO1 to resveratrol and pinpointed the possible underlying mechanism of resveratrol's inhibition effect on QS in P. aeruginosa PAO1.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Estilbenos/farmacologia , Antibacterianos/isolamento & purificação , Ciclo do Ácido Cítrico/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Metabolômica , Ressonância Magnética Nuclear Biomolecular , Estresse Oxidativo , Extratos Vegetais/química , Biossíntese de Proteínas/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Piocianina/antagonistas & inibidores , Piocianina/biossíntese , Resveratrol , Smilax/química , Estilbenos/isolamento & purificação , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/biossíntese
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