Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Interact J Med Res ; 12: e46900, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37578819

RESUMO

BACKGROUND: ChatGPT, a dialogue-based artificial intelligence language model, has shown promise in assisting clinical workflows and patient-clinician communication. However, there is a lack of feasibility assessments regarding its use for perioperative patient education in thoracic surgery. OBJECTIVE: This study aimed to assess the appropriateness and comprehensiveness of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. METHODS: This pilot study was conducted in February 2023. A total of 37 questions focused on perioperative patient education in thoracic surgery were created based on guidelines and clinical experience. Two sets of inquiries were made to ChatGPT for each question, one in English and the other in Chinese. The responses generated by ChatGPT were evaluated separately by experienced thoracic surgical clinicians for appropriateness and comprehensiveness based on a hypothetical draft response to a patient's question on the electronic information platform. For a response to be qualified, it required at least 80% of reviewers to deem it appropriate and 50% to deem it comprehensive. Statistical analyses were performed using the unpaired chi-square test or Fisher exact test, with a significance level set at P<.05. RESULTS: The set of 37 commonly asked questions covered topics such as disease information, diagnostic procedures, perioperative complications, treatment measures, disease prevention, and perioperative care considerations. In both the English and Chinese contexts, 34 (92%) out of 37 responses were qualified in terms of both appropriateness and comprehensiveness. The remaining 3 (8%) responses were unqualified in these 2 contexts. The unqualified responses primarily involved the diagnosis of disease symptoms and surgical-related complications symptoms. The reasons for determining the responses as unqualified were similar in both contexts. There was no statistically significant difference (34/37, 92% vs 34/37, 92%; P=.99) in the qualification rate between the 2 language sets. CONCLUSIONS: This pilot study demonstrates the potential feasibility of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. ChatGPT is expected to enhance patient satisfaction, reduce anxiety, and improve compliance during the perioperative period. In the future, there will be remarkable potential application for using artificial intelligence, in conjunction with human review, for patient education and health consultation after patients have provided their informed consent.

2.
BMJ Open ; 12(10): e063803, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198457

RESUMO

BACKGROUND: As one of the most common stroke sequelae, poststroke cognitive impairment significantly impacts 17.6%-83% of survivors, affecting their rehabilitation, daily living and quality of life. Improving cognitive abilities among patients in stroke recovery is therefore critical and urgent. Transcutaneous auricular vagus nerve stimulation (TAVNS) is a non-invasive, safe, cost-effective treatment with great potential for improving the cognitive function of poststroke patients. This clinical research will evaluate the effectiveness, and help elucidate the possible underlying mechanisms, of TAVNS for improving poststroke cognitive function. METHODS AND ANALYSIS: A single-centre, parallel-group, allocation concealment, assessor-blinded randomised controlled clinical trial. We will allocate 88 recruited participants to the TAVNS or sham group for an intervention that will run for 8 weeks, 5 days per week with twice daily sessions lasting 30 min each. Blood tests will be performed and questionnaires issued at baseline and 8-week and 12 week follow-ups. Primary outcomes will be changes in cognitive function scores. Secondary outcomes will be changes in activities of daily living, quality of life and serum oxidative stress indicators. ETHICS AND DISSEMINATION: The Ethics Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine has approved the protocol (No. HN-LL-YJSLW-2022200). Findings will be published in peer-reviewed academic journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200057808.


Assuntos
Disfunção Cognitiva , Acidente Vascular Cerebral , Estimulação do Nervo Vago , Atividades Cotidianas , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estimulação do Nervo Vago/métodos
3.
Biomolecules ; 10(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906402

RESUMO

Inhibition of ß-lactamases presents a promising strategy to restore the ß-lactams antibacterial activity to resistant bacteria. In this work, we found that aromatic carboxyl substituted 2-triazolylthioacetamides 1a-j inhibited VIM-2, exhibiting an IC50 value in the range of 20.6-58.6 µM. The structure-activity relationship study revealed that replacing the aliphatic carboxylic acid with aromatic carboxyl improved the inhibitory activity of 2-triazolylthioacetamides against VIM-2. 1a-j (16 mg/mL) restored the antibacterial activity of cefazolin against E. coli cell expressing VIM-2, resulting in a 4-8-fold reduction in MICs. The isothermal titration calorimetry (ITC) characterization suggested that the primary binding 2-triazolylthioacetamide (1b, 1c, or 1h) to VIM-2 was a combination of entropy and enthalpy contributions. Further, the crystal structure of VIM-2 in complex with 1b was obtained by co-crystallization with a hanging-drop vapour-diffusion method. The crystal structure analysis revealed that 1b bound to two Zn(II) ions of the enzyme active sites, formed H-bound with Asn233 and structure water molecule, and interacted with the hydrophobic pocket of enzyme activity center utilizing hydrophobic moieties; especially for the phenyl of aromatic carboxyl which formed π-π stacking with active residue His263. These studies confirmed that aromatic carboxyl substituted 2-triazolylthioacetamides are the potent VIM-2 inhibitors scaffold and provided help to further optimize 2-triazolylthioacetamides as VIM-2 even or broad-spectrum MßLs inhibitors.


Assuntos
Tioacetamida/química , Triazóis/química , beta-Lactamases/metabolismo , Antibacterianos/química , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Sítios de Ligação/fisiologia , Domínio Catalítico/fisiologia , Cristalografia por Raios X/métodos , Escherichia coli/metabolismo , Integrons/fisiologia , Cinética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Ligação Proteica/fisiologia , Relação Estrutura-Atividade , Termodinâmica , Tioacetamida/metabolismo , Triazóis/metabolismo , beta-Lactamases/química
4.
Future Med Chem ; 11(18): 2381-2394, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31544522

RESUMO

Aim: The discovery and development of novel broad-spectrum MßLs inhibitors are urgent to overcome antibiotic resistance mediated by MßLs. Methods & results: Herein, the synthesized 21 compounds exhibited potent inhibition to the clinically important MßLs (NDM-1, IMP-1 and ImiS) and effectively restored the antibacterial efficacy of cefazolin and imipenem against Escherichia coli harboring MßLs. 5b was first identified to be dual functional broad-spectrum MßLs inhibitor through assemblage of covalent and metal binding scaffold, which irreversibly inhibited B1, B2 MßLs via forming a Se-S covalent bond, and competitively inhibited B3 MßLs by coordinating the metals at active site. Conclusion: The designed compounds can serve as potent broad-spectrum MßLs inhibitors and combat MßLs-producing 'superbug' in combination with ß-lactams.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismo , Animais , Antibacterianos/síntese química , Antibacterianos/química , Calorimetria , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/química , beta-Lactamases/genética , beta-Lactamases/isolamento & purificação
5.
Anal Biochem ; 578: 29-35, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31071297

RESUMO

The d,d-dipeptidase enzyme VanX is the main cause of vancomycin resistance in gram-positive bacteria because of hydrolysis of the D-Ala-D-Ala dipeptide used in cell-wall biosynthesis. Continuous assay of VanX has proven challenging due to lack of a chromophoric substrate. Here, we report a direct approach for continuous assay of VanX in vitro and in vivo from hydrolysis of D-Ala-D-Ala, based on the heat-rate changes measured with isothermal titration calorimetry (ITC). With the ITC approach, determination of kinetic parameters of VanX hydrolyzing D-Ala-D-Ala and the inhibition constant of d-cysteine inhibitor yielded KM of 0.10 mM, kcat of 11.5 s-1, and Ki of 18.8 µM, which are consistent with the data from ninhydrin/Cd(II) assays. Cell-based ITC studies demonstrated that the VanX expressed in E. coli and in clinical strain VRE was inhibited by d-cysteine with IC50 values of 29.8 and 28.6 µM, respectively. Also, the total heat from D-Ala-D-Ala (4 mM) hydrolysis decreases strongly (in absolute value) from 1.26 mJ for VRE to 0.031 mJ for E. faecalis, which is consistent with the large MIC value of vancomycin of 512 µg/mL for VRE and the much smaller value of 4 µg/mL for E. faecalis. The ITC approach proposed here could be applied to screen and evaluate small molecule inhibitors of VanX or to identify drug resistant bacteria.


Assuntos
Proteínas de Bactérias , Calorimetria/métodos , Enterococcus faecalis/metabolismo , Escherichia coli/metabolismo , D-Ala-D-Ala Carboxipeptidase Tipo Serina , Resistência a Vancomicina/fisiologia , Enterococos Resistentes à Vancomicina/metabolismo , Proteínas de Bactérias/análise , Proteínas de Bactérias/metabolismo , Hidrólise , Cinética , D-Ala-D-Ala Carboxipeptidase Tipo Serina/análise , D-Ala-D-Ala Carboxipeptidase Tipo Serina/metabolismo , Especificidade por Substrato
6.
Chem Pharm Bull (Tokyo) ; 67(2): 135-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30713274

RESUMO

Superbug infection caused by metallo-ß-lactamases (MßLs) is a global public health threat. Previous studies reported that the thioesters specifically inhibited the B3 subclass MßL L1. In this work, nine amino acid thioesters 1-9 were synthesized, the activity evaluation revealed that all of these molecules exhibited broad-spectrum inhibitory efficacy against ImiS, IMP-1, NDM-1, and L1, with IC50 values range of 0.02-54.9 µM (except 5 and 7 on NDM-1), and 1 was found to be the best inhibitor with IC50 range of 0.02-16.63 µM. Minimal inhibitory concentration (MIC) assays showed that thioesters 1, 5 and 9 restored 2-32-fold antibacterial activity of cefazolin and/or imipenem against both Escherichia coli BL21 and DH10B strain expressing ImiS, L1, IMP-1 and NDM-1 (except 5 on NDM-1), and also, thioester 1 increased 2-4-fold antimicrobial activity of cefazolin on two clinical strains Pseudomonas aeruginosa and Klebsiella pneumoniae producing NDM-1. Stability evaluation indicated that thioester 1 was partially hydrolysed by MßLs to be converted into the mercaptoacetic acid, revealing that the thioester and its hydrolysate mercaptoacetic acid jointly inhibit MßLs. Isothermal titration calorimetry (ITC) monitoring showed that thioester 1 exhibited dose-dependent inhibition on four MßLs tested, and the binding of 1/L1 showed mainly enthalpy driven, while 1/NDM-1 was found to be more entropy driven. Docking studies suggested that 1 bound to Zn(II) ion(s) preferentially via its carboxylate group, while other moieties interacted mostly with the conserved active site residues.


Assuntos
Aminoácidos , Antibacterianos/química , Compostos de Sulfidrila/química , Inibidores de beta-Lactamases/química , beta-Lactamases , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Ésteres , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , beta-Lactamases/química
7.
ACS Infect Dis ; 4(12): 1671-1678, 2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30383355

RESUMO

The "superbug" infection caused by New Delhi metallo-ß-lactamase (NDM-1) has become an emerging threat. Monitoring NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report an isothermal titration calorimetry (ITC) method that can monitor activity and inhibition of NDM-1 in live bacterial cells in real time. This method has been exemplified by monitoring of the activity and inhibition of the target enzyme and evaluating the breakdown of antibiotics by pathogenic bacteria expressing ß-lactamases. Cell-based studies demonstrate that the NDM-1 expressed in bacterial cells was inhibited by four known inhibitors ethylene diamine tetraacetic acid (EDTA), d-captopril, ebselen and azolylthioacetamide with fifty percent inhibitory concentration (IC50) values of 3.8, 48, 0.55, and 17.5 µM, respectively, which are in good agreement with the data from inhibition kinetics using UV-vis and NMR spectroscopy in vivo. This approach could be applied to screen and evaluate small molecule inhibitors of metallo-ß-lactamases (MßLs) in whole cells or to identify drug resistant bacteria.


Assuntos
Antibacterianos/metabolismo , Calorimetria/métodos , Escherichia coli/enzimologia , Inibidores de beta-Lactamases/metabolismo , beta-Lactamases/química , beta-Lactamases/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Cefalosporinas/química , Cefalosporinas/metabolismo , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Cinética , Inibidores de beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia
8.
Mol Biosyst ; 13(11): 2323-2327, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-28906528

RESUMO

The emergence of antibiotic resistance caused by ß-lactamases, including serine ß-lactamases (SßLs) and metallo-ß-lactamases (MßLs), is a global public health threat. L1, a B3 subclass MßL, hydrolyzes almost all of known ß-lactam antibiotics. We report a simple and straightforward UV-Vis approach for real-time activity assays of ß-lactamases inside living bacterial cells, and this method has been exemplified by choosing antibiotics, L1 enzyme, Escherichia coli expressing L1 (L1 E. coli), Escherichia coli expressing extended-spectrum ß-lactamases (ESBL-E. coli), clinical bacterial strains, and reported MßL and SßL inhibitors. The cell-based studies demonstrated that cefazolin was hydrolyzed by L1 E. coli and clinical strains, and confirmed the hydrolysis to be inhibited by two known L1 inhibitors EDTA and azolylthioacetamide (ATAA), with an IC50 value of 1.6 and 18.9 µM, respectively. Also, it has been confirmed that the breakdown of cefazolin caused by ESBL-E. coli was inhibited by clavulanic acid, the first SßL inhibitor approved by FDA. The data gained through this approach are closely related to the biological function of the target enzyme in its physiological environment. The UV-Vis method proposed here can be applied to target-based whole-cell screening to search for potent ß-lactamase inhibitors, and to assays of reactions in complex biological systems, for instance in medical assays.


Assuntos
Bactérias/enzimologia , Ensaios Enzimáticos , beta-Lactamases/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Ativação Enzimática , Ensaios Enzimáticos/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Humanos , Hidrólise , Inibidores de beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia
9.
Chem Commun (Camb) ; 53(63): 8878-8881, 2017 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28737795

RESUMO

We discovered a promising metallo-ß-lactamase inhibitor, a DNA nanoribbon, by enzymatic kinetics and isothermal titration calorimetry evaluations. Atomic force microscopy, gel electrophoresis, competitive binding experiments, circular dichroic and thermal denaturation studies suggested that the DNA nanoribbon could bind to the enzyme through a minor groove.


Assuntos
DNA/farmacologia , Nanotubos de Carbono/química , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismo , DNA/química , Inibidores de beta-Lactamases/química
10.
ACS Med Chem Lett ; 8(5): 527-532, 2017 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-28523105

RESUMO

Given the clinical importance of metallo-ß-lactamases (MßLs), a new scaffold, N-substituted carbamylmethyl mercaptoacetate thioether, was constructed. The obtained molecules 1-16 inhibited MßLs from all three subclasses, but preferentially L1 from subclass B3. Compound 9 with a p-carboxyphenyl substituent exhibited the broadest spectrum with at least 70% inhibition of enzymes from all subclasses at 100 µM, while compound 5 with a p-methylphenyl substituent was the most potent inhibitor of any individual enzyme, with 97% inhibition at 100 µM and an IC50 value of 0.41 µM against L1. Isothermal titration calorimetry assays corroborate findings from UV-vis spectrophotometric assays that the inhibition of L1 by 5 is dose-dependent. Docking studies suggest that the carboxyl group, the sulfide atom, and the carbonyl group of the carbamyl coordinate Zn2 in a chelating fashion. Using E. coli cells expressing L1, 6 and 8 were able to decrease cefazolin minimum inhibitory concentration 8-fold.

11.
Trials ; 18(1): 13, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28077162

RESUMO

BACKGROUND: The management of breakthrough pain in cancer patients is always a challenge for medical professions. Occurring in 80% of cancer patients with advanced disease, breakthrough pain significantly decreases both patient's and caregiver's quality of life. The aim of this study is to assess the analgesic efficacy of a fixed inhaled nitrous oxide/oxygen mixture for adult cancer patients with breakthrough pain. METHODS/DESIGN: This is a randomized, placebo-controlled, double-blind study; it will be conducted in the General Hospital of Ningxia Medical University. The target study subjects are at least 18 years old, and are hospitalized cancer patients who are receiving routine opioids to control cancer-related pain but still experience breakthrough pain. A total of 240 patients will be recruited and randomly allocated between three treatment groups (A, B, C) and a control group (group D) in a ratio of 3:1. All treatment groups (A, B, C) will receive standard pain treatment (oral immediate-release morphine) plus a pre-prepared nitrous oxide/oxygen mixture, and the control group (D) will receive the standard pain treatment plus oxygen. Patients, doctors, nurses, and data collectors are all blind to the experiment. Assessments will be taken before treatment (T0), at 5 min (T1) and 15 min (T2) during treatment, and at 5 min after treatment (T3). The primary endpoint measures will be the percentage of patients whose pain is relieved at T1, T2, and T3. Secondary outcome measures will include the safety of treatment, adverse events, and satisfaction from both health professionals and patients. DISCUSSION: This study aims to provide an effective and practical intervention for a fast breakthrough pain relief and to improve cancer patients' quality of life significantly. The Evidence-Based Medicine Working Group claim that a randomized, double-blind, placebo-controlled experimental intervention is the most appropriate design to demonstrate its efficacy, so this study could give a new approach to controlling breakthrough pain episodes. TRIAL REGISTRATION: ChiCTR-INC-16008075 . Registered on 8 March 2016.


Assuntos
Analgésicos/administração & dosagem , Dor Irruptiva/tratamento farmacológico , Neoplasias/complicações , Óxido Nitroso/administração & dosagem , Oxigenoterapia , Administração por Inalação , Analgésicos/efeitos adversos , Dor Irruptiva/diagnóstico , Dor Irruptiva/etiologia , China , Protocolos Clínicos , Método Duplo-Cego , Humanos , Neoplasias/diagnóstico , Óxido Nitroso/efeitos adversos , Oxigenoterapia/efeitos adversos , Medição da Dor , Satisfação do Paciente , Qualidade de Vida , Projetos de Pesquisa , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 37(3): 326-330, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30650484

RESUMO

Objective To observe the effect of needle pricking therapy on rheological indices and efficacy for infertile patients with varicocele (VC). Methods A total of 215 infertility patients with VC were assigned to the treatment group (109 cases, treated by needle pricking therapy) and the control group (106 cases, treated by drug therapy). Patients in the treatment group received CHEN's needle pricking therapy, once per week for a total of 10 times. Those in the control group took Guizhi Fuling Cap- sule (GFC), 0. 31g/pill, 3 pills each time, three times per day for 70 successive days. The diameter of VC, whole blood apparent viscosity, and plasma viscosity value were detected in the two groups after 75- day treatment. Sperm count, sperm motility rate, sperm motility, teratopermia rate, and other parame- ters were determined to evaluate the efficacy. Routines of blood, urine, and stool were detected. Renal and liver functions were examined to evaluate the safety. Results Compared with before treatment in the same group, the diameter of VC was narrowed in grade I and II patients of the two groups after treatment (P <0.05). The diameter of VC was obviously narrower in grade II patients of the treatment group after treatment (P <0. 01). Compared with before treatment in the same group, semen quality was improved in the two groups after treatment (P <0. 05,P <0.01). Besides, sperm density was reduced, sperm motility rate was elevated, spermatozoa with normal morphology was increased with longer fluidized time in the treatment group after treatment, which were all better than those of the control group (P <0.05). Compared with before treatment, whole blood apparent viscosity and plasma viscosity value both obviously decreased in the treatment group after treatment (P <0. 05). The total effective rate was better in the treatment group than in the control group (P <0. 05). Conclusion Needle pricking therapy could obviously improve blood flow and vasomotic elasticity of infertile patients with VC, lower plasma viscosity, thus promoting blood circulation and lowering VC.


Assuntos
Terapia por Acupuntura , Infertilidade Masculina , Varicocele , Humanos , Infertilidade Masculina/complicações , Infertilidade Masculina/terapia , Masculino , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides , Varicocele/complicações
13.
Oncotarget ; 8(3): 4796-4813, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27902475

RESUMO

BACKGROUND AND PURPOSE: As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. EXPERIMENTAL APPROACH: The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested. KEY RESULTS: Osthole (20, 40 mg·kg-1) group can greatly attenuate the changes of the score and kidney histopathology damage and enhance the survival time of septic mice. After the CLP surgery, degrees of SCr and BUN related to kidney injury were upregulated. The concentrations of SCr and BUN can be greatly reduced by treatment with osthole. Furthermore, osthole could increase bacterial killing activity and phagocytic activities of macrophages impaired after CLP partly and attenuate blood bacterial counts and leukocyte infiltration markedly. Furthermore, osthole can suppress NF-κB signal pathway through the inhibition of the nuclear translocation by regulating phosphorylation of IκBα and IKKß and hinder the production of chemoattractant (MCP-1 and IL-8) and proinflammatory cytokines (TNF-α, IL-1ß and IL-6). CONCLUSION AND IMPLICATIONS: Mainly because of its immunomodulatory properties and anti-inflammatory activity, which might be closely associated with suppression of the stimulation of the NF-κB signal pathway, osthole has protective effect on sepsis-induced kidney injury. It can be seen from such evidence that osthole can be potentially applied in the treatment of acute kidney injury.


Assuntos
Injúria Renal Aguda/prevenção & controle , Anti-Inflamatórios/administração & dosagem , Cumarínicos/administração & dosagem , Sepse/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Cumarínicos/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , NF-kappa B/metabolismo , Células RAW 264.7 , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
14.
Bioorg Med Chem Lett ; 26(19): 4698-4701, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27595424

RESUMO

The emergence of antibiotic resistance caused by metallo-ß-lactamases (MßLs) is a global public health problem. Recently, we found amino acid thioesters to be a highly promising scaffold for inhibitors of the MßL L1. In order to optimize this series of inhibitors, nine new amino acid thioesters were developed by modifying the substituents on the N-terminus of the thioesters and the groups representing the amino acid side chain. Biological activity assays indicate that all of them are very potent inhibitors of L1 with an IC50 value range of 20-600nM, lower than those of most of the previously reported inhibitors of this scaffold. Analysis of structure-activity relationship reveals that big hydrophobic substituents on the N-terminus and a methionine amino acid side chain improves inhibitory activity of the thioesters. All these inhibitors are able to restore antibacterial activity of a ß-lactam antibiotic against Escherichia coli BL21(DE3) cells producing L1 to that against E. coli cells lacking a ß-lactamase. Docking studies reveal that a large N-terminal hydrophobic group results in a slightly different binding mode than smaller hydrophobic groups at the same position.


Assuntos
Aminoácidos/química , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/efeitos dos fármacos , Ésteres , Relação Estrutura-Atividade
15.
Zhonghua Bing Li Xue Za Zhi ; 39(6): 405-9, 2010 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21055159

RESUMO

OBJECTIVE: To study the effect of PKC signalling pathway and aldose reductase (AR) on the expression of fibronectin (FN) induced by transforming growth factor-ß1 (TGF-ß1). METHODS: Human mesangial cells (HMCs) were cultured and transfected with pcDNA3-AR, and subject to AR gene silencing with small interfering RNA (siRNA) and then the cell was treated with recombinant human TGF-ß1. The AR mRNA expression in the HMCs was examined using real time RT-PCR and protein expression of AR and FN was detected by Western blotting. RESULTS: The cultured HMC treated with TGF-ß1 showed increased expression of AR and FN, the normal HMC showed not reduced expression of FN after incubation with single inhibitors of AR.Pre-incubation of cells with inhibitors of AR and PKC, then the different groups of cells were treated with TGF-ß1, and the induction effect on FN expression was suppressed (34%) in HMC. HMCs transfected with AR showed a strong protein expression of FN, which was increased by 3.6-fold after treatment with TGF-ß1 (P < 0.05), and the induction effect on FN expression was suppressed by GÖ6983 (42%) in HMCs (P < 0.05). The HMC with AR gene knock-down by siRNA showed a decreased expression of AR and 90% decrease of FN protein in HMCs (P < 0.01), and TGF-ß1-induced up-regulation of FN was significantly suppressed by siRNA (12%) in HMCs (P < 0.01). CONCLUSIONS: AR is capable of regulating FN expression only in the presence of TGF-ß1, and this reaction is possibly accomplished through the activation of PKC signalling pathway.


Assuntos
Aldeído Redutase/biossíntese , Fibronectinas/metabolismo , Células Mesangiais/metabolismo , Proteína Quinase C , Fator de Crescimento Transformador beta1/farmacologia , Aldeído Redutase/antagonistas & inibidores , Aldeído Redutase/genética , Benzotiazóis/farmacologia , Carbazóis/farmacologia , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Indóis , Maleimidas , Células Mesangiais/citologia , Ftalazinas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais , Transfecção , Regulação para Cima
16.
Zhen Ci Yan Jiu ; 34(5): 344-8, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20128296

RESUMO

OBJECTIVE: To observe the effect of needle-pricking bleeding combined with pulling-rotating manipulation and simple manipulation on blood rheology in vertebral artery type cervical spondylosis (VATCS) patients, so as to analyze their mechanisms in relieving VATCS. METHODS: A total of 198 VATCS patients were randomly divided into treatment group (n=101) which was treated with needle-pricking plus pulling-rotating manipulation, and control group (n=97) which was treated with simple pulling-rotating manipulation, according to the random number table. The treatment was given once every 7 days, 9 times altogether. The peak systolic blood flow velocity (Vpeak), end-diastolic blood velocity (Vmin), pulsatility index (PI) and resistent index (RI) of bilateral vertebral arteries (VA) and basilar artery (BA) were detected by transcranial doppler sonography (TCD). Whole blood apparent viscosity and the plasma viscosity in the treatment group were determined by using a blood viscosimeter. RESULTS: Of the 101 and 97 VATCS cases in the treatment and control groups, 62 (61.38%) and 12 (12.37%) were cured basically, 23 (22.77%) and 26 (26.80%) experienced marked improvement, 14 (13.86%) and 41 (42.27%) were improved. 2 (1.98%) and 18 (18.55%) failed in the treatment, with the total effective rates being 98.01% and 81.44% separately. The effective rate of the treatment group was significantly higher than that of control group (P<0.05). Compared with pretreatment, Vpeak and Vmin of the bilateral VA and BA in the treatment group, and Vpeak of the right VA in the control group increased significantly (P<0.01, P<0.05), PI and RI of the bilateral VA and BA in the treatment group, and PI and RI of the right VA in the control group decreased significantly (P<0.01, P<0.05), suggesting a marked reduction of the vascular resistance and an apparent increase of the cerebral blood supply after the treatment. The therapeutic effects of the above-mentioned indexes of treatment group were significantly superior to those of the control group (P<0.05). In comparison with pre-treatment, the whole blood apparent viscosity (high, medium and low shear rates) and plasma viscosity of the treatment group post-treatment were obviously reduced (P<0.01, P<0.05). CONCLUSION: Needle-pricking therapy combined with pulling-rotating manipulation can significantly improve VATCS patients' clinical symptoms, which may be closely related to its effects in lowering vascular blood resistance and blood viscosity and increasing cerebral blood supply.


Assuntos
Terapia por Acupuntura , Espondilose/terapia , Artéria Vertebral/fisiopatologia , Adulto , Viscosidade Sanguínea , Feminino , Humanos , Masculino , Reologia , Espondilose/diagnóstico por imagem , Espondilose/fisiopatologia , Ultrassonografia Doppler Transcraniana , Artéria Vertebral/diagnóstico por imagem
17.
Zhongguo Zhen Jiu ; 26(6): 389-91, 2006 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-16813177

RESUMO

OBJECTIVE: To search for the best method for increasing clinical therapeutic effect on primary abnormality of sperm. METHODS: One hundred and sixty-eight cases of infertility were randomly divided into a treatment group of 85 cases and a control group of 83 cases. The treatment group were treated with needle-picking at bilateral Shengzhi points, Dicong Shenjing points and L2 Shenjing points as main. The control group were treated with oral administration of Wuzi Yanzong Pills [symbol: see text]. Their therapeutic effects were observed in 3 hospitals. RESULTS: The total effective rate of 83.5% and the pregnancy rate of the patient's wife of 78.8% in the treatment group, and corresponding figures were 54.2% and 43.4% in the control group, with a very significant difference between the two groups (P < 0.01); and reproductive hormones improved significantly after treatment in the two groups (P < 0.01); after treatment, superoxide dismulase (SOD) activity and Zn content in semen were elevated and cadmium level decreased significantly in the treatment group (P < 0.05). CONCLUSION: Needle picking therapy can significantly improve and regulate endocrine function, increase quality of semen and elevate pregnancy rate of the patient's wife for the patient of primary abnormal sperm.


Assuntos
Terapia por Acupuntura , Infertilidade Masculina/terapia , Adulto , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Contagem de Espermatozoides
18.
Yi Chuan Xue Bao ; 33(1): 32-40, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16450585

RESUMO

The Drosophila dorsal vessel is a segmentally repeated linear organ, in which seven-up (svp) is expressed in two pairs of cardioblasts and two pairs of pericardial cells in each segment. Under the control of hedgehog (hh) signaling from the dorsal ectoderm, svp participates in diversifying cardioblast identities within each segment. In this experiment, the homozygous embryos of svp mutants exhibited an increase in cell size of Eve positive pericardial cells (EPCs) and a disarranged expression pattern, while the cardioblasts pattern of svp-lacZ expression was normal. In the meantime, the DAI muscle founders were absent in some segments in svp mutant embryos, and the dorsal somatic muscle patterning was also severely damaged in the late stage mutant embryos, suggesting that svp is required for the differentiation of Eve-positive pericardial cells and DA1 muscle founders and may have a role in EPC cell growth.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Drosophila/citologia , Embrião não Mamífero/citologia , Pericárdio/citologia , Receptores de Esteroides/fisiologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Drosophila/embriologia , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiologia , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/fisiologia , Homozigoto , Imuno-Histoquímica , Hibridização In Situ , Músculos/citologia , Músculos/embriologia , Músculos/metabolismo , Mutação , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/metabolismo , Pericárdio/embriologia , Pericárdio/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...