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1.
Acta Biomater ; 182: 275-287, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38761960

RESUMO

Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. STATEMENT OF SIGNIFICANCE: This study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Níquel , Oxigênio , Níquel/química , Níquel/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Oxigênio/química , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/terapia , Terapia Fototérmica , Biofilmes/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/uso terapêutico , Fototerapia
2.
Adv Sci (Weinh) ; 10(13): e2207507, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36847061

RESUMO

With the threat posed by drug-resistant pathogenic bacteria, developing non-antibiotic strategies for eradicating clinically prevalent superbugs remains challenging. Ferroptosis is a newly discovered form of regulated cell death that can overcome drug resistance. Emerging evidence shows the potential of triggering ferroptosis-like for antibacterial therapy, but the direct delivery of iron species is inefficient and may cause detrimental effects. Herein, an effective strategy to induce bacterial nonferrous ferroptosis-like by coordinating single-atom metal sites (e.g., Ir and Ru) into the sp2 -carbon-linked covalent organic framework (sp2 c-COF-Ir-ppy2 and sp2 c-COF-Ru-bpy2 ) is reported. Upon activating by light irradiation or hydrogen peroxide, the as-constructed Ir and Ru single-atom catalysts (SACs) can significantly expedite intracellular reactive oxygen species burst, enhance glutathione depletion-related glutathione peroxidase 4 deactivation, and disturb the nitrogen and respiratory metabolisms, leading to lipid peroxidation-driven ferroptotic damage. Both SAC inducers show potent antibacterial activity against Gram-positive bacteria, Gram-negative bacteria, clinically isolated methicillin-resistant Staphylococcus aureus (MRSA), and biofilms, as well as excellent biocompatibility and strong therapeutic and preventive potential in MRSA-infected wounds and abscesses. This delicate nonferrous ferroptosis-like strategy may open up new insights into the therapy of drug-resistant pathogen infection.


Assuntos
Ferroptose , Estruturas Metalorgânicas , Staphylococcus aureus Resistente à Meticilina , Domínio Catalítico , Antibacterianos/farmacologia
3.
Small ; 19(4): e2205471, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399641

RESUMO

The emergence and evolution of antimicrobial resistance (AMR) pose a significant challenge to the current arsenal to fight infection. Antibiotic adjuvants represent an appealing tactic for tackling the AMR of pathogens, however, their practical applications are greatly constrained by the harsh infectious microenvironment. Herein, it is found that silver nanoclusters (Ag NCs) can possess tunable enzymatic activities to modulate infectious microenvironments. Based on this finding, an enzymatic nanoadjuvant (EnzNA) self-assembled from Ag NCs, which is inert under neutral physiological conditions but can readily disassemble into isolated Ag NCs exhibiting biofilm destructive oxidase-mimetic activity in the acidic biofilm microenvironment, is developed. Once internalized into the neutral cytoplasm of bacteria, Ag NCs switch to reveal the thiol oxidase-mimetic activity to suppress ribosomal biogenesis for AMR reversal and evolution inhibition of pathogens. Consequently, EnzNAs revitalize various existing antibiotics against methicillin-resistant Staphylococcus aureus, and potentiate the antibiotic efficacy against biofilm-mediated skin infection and lethal lung infection in mice. These findings highlight the capability of enzyme-mimetic nanomaterials to modulate the infectious microenvironment and potentiate antibiotics, providing a paradigm shift for anti-infection therapy.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Animais , Camundongos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Bactérias , Biofilmes , Testes de Sensibilidade Microbiana
4.
Pharmaceutics ; 14(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36365168

RESUMO

Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention worldwide due to its wide application in different areas, including medicine. Based on the important biological roles of cobalt, cobalt nanomaterials have recently been widely developed for their attractive biomedical applications. With advantages such as low costs in preparation, hypotoxicity, photothermal conversion abilities, and high drug loading ability, cobalt nanomaterials have been proven to show promising potential in anticancer and anti-infection treatment. In this review, we summarize the characters of cobalt nanomaterials, followed by the advances in their biological functions and mechanisms. More importantly, we emphatically discuss the potential of cobalt nanomaterials as anti-infectious agents, drug carriers, and immunomodulators for anti-infection treatments, which might be helpful to facilitate progress in future research of anti-infection therapy.

5.
Adv Drug Deliv Rev ; 186: 114340, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35569561

RESUMO

Research on bacterial membrane vesicles (BMVs) is an emerging topic, and the goal is to address whether BMVs can bring translational tools to improve current therapies. In this review, we provided the updated studies on BMVs including their production, their types, and therapeutic regimens for treating infectious diseases and cancers. We described several platforms of BMVs, such as outer membrane vesicles (OMVs), inner membrane vesicles (IMVs) and double membrane vesicles (DMVs), and those structures were produced from Gram-negative or Gram-positive bacteria. We also discussed how to engineer and formulate new and novel BMVs using chemical, physical, and genetic methods. For therapies, we analyzed current methods for loading drugs in BMVs and discussed their limitations. Finally, we reviewed several therapeutic platforms of BMVs that have been exploited in improving the treatments of infectious diseases and cancers. Although BMVs offer the promising biomedical applications, it is needed to develop rigorous approaches and methods to generate reproducible and scalable drug delivery systems for translation.


Assuntos
Doenças Transmissíveis , Neoplasias , Bactérias , Membrana Celular , Doenças Transmissíveis/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico
6.
Front Pharmacol ; 12: 682284, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393776

RESUMO

Infectious diseases, caused by the direct exposure of cellular or acellular pathogens, are found to be closely associated with multiple inflammation and immune responses, keeping one of the top threats to human health. As an indispensable trace element, Selenium (Se) plays important roles in antioxidant defence and redox state regulation along with a variety of specific metabolic pathways. In recent decades, with the development of novel nanotechnology, Selenium nanoparticles (Se NPs) emerged as a promising agent for biomedical uses due to their low toxicity, degradability and high bioavailability. Taking the advantages of the strong ability to trigger apoptosis or autophagy by regulating reactive oxygen species (ROS), Se NPs have been widely used for direct anticancer treatments and pathogen killing/clearance in host cells. With excellent stability and drug encapsulation capacity, Se NPs are now serving as a kind of powerful nano-carriers for anti-cancer, anti-inflammation and anti-infection treatments. Notably, Se NPs are also found to play critical roles in immunity regulations, such as macrophage and T effector cell activation, which thus provides new possibilities to achieve novel nano-immune synergetic strategy for anti-cancer and anti-infection therapies. In this review, we summarized the progress of preparation methods for Se NPs, followed by the advances of their biological functions and mechanisms for biomedical uses, especially in the field of anti-infection treatments. Moreover, we further provide some prospects of Se NPs in anti-infectious diseases, which would be helpful for facilitating their future research progress for anti-infection therapy.

7.
J Int Med Res ; 48(10): 300060520965843, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33131370

RESUMO

Here, we report a case of an infectious pseudoaneurysm at the root of the innominate artery, compressing the trachea, that resulted in massive hemorrhage due to rupture of the innominate artery. The patient, a 31-year-old man, had complained of persistent fever for 40 days and severe dyspnea for 1 week. Contrast-enhanced computed tomography imaging of neck and thorax showed a pseudoaneurysm originating from the root of the innominate artery that was severely compressing the main trachea. A hybrid surgery strategy was applied. We first implanted a covered stent in the root of the innominate artery. Then, we performed a left-to-right carotid-carotid bypass with a great saphenous vein graft. Finally, we performed a median thoracotomy in which both the pseudoaneurysm and the previously implanted covered stent were successfully extracted. The patient lost strength in the right upper limb muscle on postoperative day 2 but recovered to baseline strength after 3 months. A hybrid surgical technique may represent a practical solution for such conditions.


Assuntos
Falso Aneurisma , Tronco Braquiocefálico , Adulto , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Tronco Braquiocefálico/diagnóstico por imagem , Tronco Braquiocefálico/cirurgia , Humanos , Masculino , Stents , Traqueia/diagnóstico por imagem , Traqueia/cirurgia , Resultado do Tratamento
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-609005

RESUMO

Objective To describe clinical characteristics and anti-infective treatment of Listeria monocytogenes(L.monocytogenes)meningitis.Methods Clinical manifestations and cerebrospinal fluid(CSF)examination results of 6 patients with L.monocytogenes meningitis in a hospital were analyzed retrospectively.Evaluation methods were developed according to relevant guidelines and literatures,anti-infective treatment and prognosis of patients with L.monocytogenes meningitis were evaluated.Results Two of 4 adults with L.monocytogenes meningitis had triad of fever,stiff neck,and altered mental status,the mean white blood cell count(WBC)of the initial CSF detection was 997×106/L,CSF/blood glucose ratio was 0.32,CSF protein was 1.43g/L;the other 2 neonates had fever,epilepsy,and hyponatremia,WBC were both>1 000×106/L,CSF protein were both>1 g/L,CSF/blood glucose ratio was<0.5.Of 6 patients,none were treated with appropriate initial empiric anti-infection therapy,confirmed by CSF or blood culture,5 cases were treated with ampicillin anti-infective therapy,1 used compound sulfamethoxazole due to penicillin allergy;1 neonate died,1 elderly patient was with moderate disability,the remaining 4 cases were all recovered and discharged from hospital.Conclusion Clinical manifestations and CSF findings of L.monocytogenes meningitis are not different from other purulent meningitis,commonly used antimicrobial agents for the treatment of purulent meningitis are not sensitive to L.monocytogenes,which should be paid attention in clinic.

9.
China Pharmacist ; (12): 1906-1908, 2016.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-503269

RESUMO

Objective:To analyze the anti-infection therapy for one lung cancer patient with agranulocytosis and fever after chemo-therapy to provide pharmaceutical care and support for the rational anti-infection drug use in the patient. Methods: Clinical pharma-cists analyzed the drugs used in the patient and provided pharmaceutical care for doctors according to the examination results and diag-nosis of the patient. Results:By participating in the treatment plan, clinical pharmacists ensured the treatment for the patient was safe and effective. Conclusion:Clinical pharmacists should assist doctors in making out the treatment plan according to patients’ situation in order to promote rational drug use in clinics and reflect the value of pharmaceutical care.

10.
China Pharmacist ; (12): 1156-1157,1169, 2016.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-604338

RESUMO

Objective:To analyze the pharmaceutical care performed by clinical pharmacist for one patient with biliary tract infec -tion to investigate the role of clinical pharmacists in clinical treatment .Methods:The clinical pharmacist supervised the whole process of treatment for the patient and optimized the treatment regimen together with the clinical doctors to achieve good efficacy .Results:With the cooperation of clinical pharmacist , the clinical doctors changed the treatment drugs to avoid the potential adverse drug reac -tions until the patient was cured .Conclusion:The participation of clinical pharmacist in the pharmaceutical care for the patients with biliary tract infection can provide a new thought of working mode .

11.
China Pharmacist ; (12): 624-627, 2015.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-669967

RESUMO

Objective:To analyze the characteristics of infectious diseases from neurology ward and provide reference for the treat-ment. Methods:The consultation record of the neurological patients who suffered infection diseases were retrospectively summarized from January 2011 to December 2013. All the consultation were performed by clinical pharmacists. SPSS 19. 0 software was used to an-alyze the adoption and prognosis of the outcomes. Results:In 439 consultation cases,256 patients(58. 31%)were older than 65 years. Most of the cases were respiratory infection(294 cases,65. 33%),urinary tract infection(40 cases,8. 89%)and intracranial infection(37 cases,8. 22%). There were 510 strains of bacteria isolated by culturing,in which 362 strains were gram-negative bacte-ria(70. 98%),127 strains were gram-positive bacteria(24. 90%)and 21 strains were fungi(4. 12%). The top five of pathogenic bac-teria were Pseudomonas aeruginosa(125 stains,24. 51%),Acinetobacter baumannii(93 stains,18. 24%),Staphylococcus aureus(88 stains,17. 25%),Staphylococcus aureus(68 stains,13. 33%)and Escherichia coli. (32 stains,6. 27%). The detection rates of ESBLs of K. pneumonia and E. coli were 61. 36% and 75. 00%,respectively. Among 125 strains of P. aeruginosa,the sensitive rate to meropenem and inipenem was 65. 8% and 70. 6%,respectively. A. baumannii was highly multidrug resistant,and 21 strains (22. 58%)with pan-drug resistance were isolated. Gram-positive bacteria were highly sensitive to vancomycin and teicoplanin. Totally 35 strains(52. 24%)of MRSA were isolated. The complete adoption rate of consultation opinion was 84. 74%(372 cases),the partial adoption rate was 7. 28%(32 cases),and 35 cases(7. 97%)were declined. In all the adopted cases(319 cases,78. 96%)showed effectiveness. In the linear correlation analysis,the consultation adoption and therapy outcomes had significant correlation(P<0. 01). Conclusion:Clinical pharmacists can improve the efficiency in anti-infection therapy and play important roles in the treatment of infec-tious diseases in neurology ward,especially in the treatment of drug-resistant bacterial infections.

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