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1.
J Coll Physicians Surg Pak ; 34(6): 682-687, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840351

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of eribulin plus anti-angiogenic medicine in metastatic breast cancer (MBC), and explore the potential biomarkers. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology, Xi'an International Medical Centre Hospital, Xi'an, China, from May 2022 to 2023. METHODOLOGY: A total of 40 MBC patients treated with eribulin were enrolled. Patients were divided into two groups based on whether they received eribulin monotherapy or combined therapy. Median progression-free survival (mPFS), the time from the start of erbium treatment to the time of disease progression, was calculated using the Kaplan-Meier method. RESULTS: The eribulin plus anti-angiogenic medicine treatment group had a significantly prolonged mPFS compared to the group without anti-angiogenic medicine treatment (7.0 months vs. 2.0 months, p <0.001). The multivariate analysis identified that the combination of anti-angiogenic therapy (HR = 0.043, p = 0.004) and the occurrence of grade 3-4 neutropenia after the treatment were two predictive factors for longer PFS (HR = 0.322, p = 0.009). In contrast, prior resistance to taxane was predictive of shorter PFS (HR = 4.583, p = 0.019). Other clinic-pathological factors were not significantly associated with PFS. Fisher's exact test showed no significant increase in treatment-related adverse events (all grades) after combination with anti-angiogenic medicine. CONCLUSION: The eribulin plus anti-angiogenic combination may act as a potential therapy for late-line MBC patients with clinically beneficial therapeutic effects. KEY WORDS: Metastatic breast cancer, Eribulin, Anti-angiogenic therapy, Predictive indicators of efficacy.


Assuntos
Inibidores da Angiogênese , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Furanos , Cetonas , Humanos , Furanos/uso terapêutico , Cetonas/uso terapêutico , Cetonas/efeitos adversos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Idoso , Metástase Neoplásica , Resultado do Tratamento , Intervalo Livre de Progressão , China , Policetídeos de Poliéter
2.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(3): 251-256, 2024 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-38863089

RESUMO

Polyetheretherketone (PEEK) has emerged as a thermoplastic material of choice in the realm of implantable medical devices, owing to its high biocompatibility and exceptional mechanical strength. Despite its promise for custom-made medical devices, 3D-printed PEEK in orthopedics, trauma, and spinal implants has not yet achieved widespread application. This study outlines the properties of PEEK, 3D-printed PEEK-based composites, and their utilization in implantable medical devices, thereby fostering the development and regulation of next-generation medical devices.


Assuntos
Benzofenonas , Materiais Biocompatíveis , Cetonas , Polietilenoglicóis , Polímeros , Impressão Tridimensional , Próteses e Implantes , Humanos
3.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(3): 237-244, 2024 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-38863087

RESUMO

Additive manufacturing (3D printing) technology aligns with the direction of precision and customization in future medicine, presenting a significant opportunity for innovative development in high-end medical devices. Currently, research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants. Primary areas including metallic orthopaedic implants, polyether-ether-ketone (PEEK) bone implants, and biodegradable implants have been developed for clinical and industrial application. Recent research achievements in these areas are reviewed, with a discussion on the additive manufacturing technologies and applications for customized implants. Challenges faced by different types of implants are analyzed from technological, application, and regulatory perspectives. Furthermore, prospects and suggestions for future development are outlined.


Assuntos
Impressão Tridimensional , Próteses e Implantes , Benzofenonas , Polímeros , Humanos , Cetonas , Desenho de Prótese , Materiais Biocompatíveis , Polietilenoglicóis , Implantes Absorvíveis
4.
Carbohydr Res ; 541: 109167, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823063

RESUMO

This paper describes a mild and efficient catalytic deprotection method for isopropylidene ketals and benzylidene acetals using AcOH/H2O/DME(1,2-Dimethoxyethane). The method effectively removes ketal and acetal protecting groups from 2-deoxyglycosides which are prone to hydrolysis under acidic conditions. Moreover, it enables the selective removal of the terminal ketal over an internal one.


Assuntos
Glicosídeos , Glicosídeos/química , Glicosídeos/síntese química , Água/química , Estereoisomerismo , Cetonas/química , Catálise , Acetais/química , Estrutura Molecular
6.
Nature ; 629(8013): 824-829, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720081

RESUMO

Enzymes play an increasingly important role in improving the benignity and efficiency of chemical production, yet the diversity of their applications lags heavily behind chemical catalysts as a result of the relatively narrow range of reaction mechanisms of enzymes. The creation of enzymes containing non-biological functionalities facilitates reaction mechanisms outside nature's canon and paves the way towards fully programmable biocatalysis1-3. Here we present a completely genetically encoded boronic-acid-containing designer enzyme with organocatalytic reactivity not achievable with natural or engineered biocatalysts4,5. This boron enzyme catalyses the kinetic resolution of hydroxyketones by oxime formation, in which crucial interactions with the protein scaffold assist in the catalysis. A directed evolution campaign led to a variant with natural-enzyme-like enantioselectivities for several different substrates. The unique activation mode of the boron enzyme was confirmed using X-ray crystallography, high-resolution mass spectrometry (HRMS) and 11B NMR spectroscopy. Our study demonstrates that genetic-code expansion can be used to create evolvable enantioselective enzymes that rely on xenobiotic catalytic moieties such as boronic acids and access reaction mechanisms not reachable through catalytic promiscuity of natural or engineered enzymes.


Assuntos
Biocatálise , Ácidos Borônicos , Enzimas , Engenharia de Proteínas , Ácidos Borônicos/química , Ácidos Borônicos/metabolismo , Cristalografia por Raios X , Evolução Molecular Direcionada , Enzimas/química , Enzimas/metabolismo , Enzimas/genética , Cetonas/química , Cetonas/metabolismo , Cinética , Modelos Moleculares , Oximas/química , Oximas/metabolismo , Especificidade por Substrato , Ressonância Magnética Nuclear Biomolecular , Espectrometria de Massas , Xenobióticos/química , Xenobióticos/metabolismo
7.
Biomater Adv ; 161: 213888, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759305

RESUMO

Short carbon fiber (SCF) reinforced polymer composites are expected to possess outstanding biotribological and mechanical properties in certain direction, while the non-oriented SCF weakens its reinforcing effect in the matrix. In this work, high-oriented SCF was achieved during nozzle extrusion, and then SCF reinforced polyether-ether-ketone (PEEK) composites were fabricated by fused deposition modeling (FDM). The concrete orientation process of SCF was theoretically simulated, and significant shear stress difference was generated at both ends of SCF. As a result, the SCF was distributed in the matrix in a hierarchical structure, containing surface layer I, II and core layer. Moreover, the SCF was oriented highly along the printing direction and demonstrated a more competitive orientation distribution compared to other studies. The SCF/PEEK composites showed a considerable improvement in wear resistance by 44 % due to self-lubricating and load-bearing capability of SCF. Besides, it demonstrated enhancements in Brinell hardness, compressive and impact strength by 48.52 %, 16.42 % and 53.64 %, respectively. In addition, SCF/PEEK composites also showed good cytocompatibility. The findings gained herein are useful for developing the high-oriented SCF reinforced polymer composites with superior biotribological and mechanical properties for artificial joints.


Assuntos
Benzofenonas , Fibra de Carbono , Cetonas , Teste de Materiais , Polietilenoglicóis , Polímeros , Impressão Tridimensional , Fibra de Carbono/química , Polímeros/química , Polietilenoglicóis/química , Cetonas/química , Teste de Materiais/métodos , Materiais Biocompatíveis/química , Prótese Articular , Humanos
8.
Bioorg Chem ; 148: 107453, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761708

RESUMO

Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC50 = 4.55 ± 0.92 µM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA2 was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA2, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA2. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA2/COX-2/PGE2 and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA2 and COX-2 are implicated in the pathophysiology.


Assuntos
Artrite Reumatoide , Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2 , Animais , Camundongos , Ciclo-Oxigenase 2/metabolismo , Artrite Reumatoide/tratamento farmacológico , Células RAW 264.7 , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/síntese química , Ratos , Relação Estrutura-Atividade , Estrutura Molecular , Inflamação/tratamento farmacológico , Masculino , Relação Dose-Resposta a Droga , Cetonas/química , Cetonas/farmacologia , Cetonas/síntese química , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese química , Fosfolipases A2/metabolismo , Administração Oral , Ratos Sprague-Dawley
9.
Cancer Res Commun ; 4(6): 1430-1440, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38717161

RESUMO

The PI3K pathway regulates essential cellular functions and promotes chemotherapy resistance. Activation of PI3K pathway signaling is commonly observed in triple-negative breast cancer (TNBC). However previous studies that combined PI3K pathway inhibitors with taxane regimens have yielded inconsistent results. We therefore set out to examine whether the combination of copanlisib, a clinical grade pan-PI3K inhibitor, and eribulin, an antimitotic chemotherapy approved for taxane-resistant metastatic breast cancer, improves the antitumor effect in TNBC. A panel of eight TNBC patient-derived xenograft (PDX) models was tested for tumor growth response to copanlisib and eribulin, alone or in combination. Treatment-induced signaling changes were examined by reverse phase protein array, immunohistochemistry (IHC) and 18F-fluorodeoxyglucose PET (18F-FDG PET). Compared with each drug alone, the combination of eribulin and copanlisib led to enhanced tumor growth inhibition, which was observed in both eribulin-sensitive and -resistant TNBC PDX models, regardless of PI3K pathway alterations or PTEN status. Copanlisib reduced PI3K signaling and enhanced eribulin-induced mitotic arrest. The combination enhanced induction of apoptosis compared with each drug alone. Interestingly, eribulin upregulated PI3K pathway signaling in PDX tumors, as demonstrated by increased tracer uptake by 18F-FDG PET scan and AKT phosphorylation by IHC. These changes were inhibited by the addition of copanlisib. These data support further clinical development for the combination of copanlisib and eribulin and led to a phase I/II trial of copanlisib and eribulin in patients with metastatic TNBC. SIGNIFICANCE: In this research, we demonstrated that the pan-PI3K inhibitor copanlisib enhanced the cytotoxicity of eribulin in a panel of TNBC PDX models. The improved tumor growth inhibition was irrespective of PI3K pathway alteration and was corroborated by the enhanced mitotic arrest and apoptotic induction observed in PDX tumors after combination therapy compared with each drug alone. These data provide the preclinical rationale for the clinical testing in TNBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Furanos , Cetonas , Pirimidinas , Neoplasias de Mama Triplo Negativas , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Cetonas/farmacologia , Cetonas/administração & dosagem , Cetonas/uso terapêutico , Animais , Furanos/farmacologia , Furanos/administração & dosagem , Furanos/uso terapêutico , Humanos , Feminino , Camundongos , Pirimidinas/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Quinazolinas/farmacologia , Quinazolinas/administração & dosagem , Quinazolinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Policetídeos de Poliéter
10.
J Chem Inf Model ; 64(11): 4462-4474, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38776464

RESUMO

The (S)-norcoclaurine synthase from Thalictrum flavum (TfNCS) stereoselectively catalyzes the Pictet-Spengler reaction between dopamine and 4-hydroxyphenylacetaldehyde to give (S)-norcoclaurine. TfNCS can catalyze the Pictet-Spengler reaction with various aldehydes and ketones, leading to diverse tetrahydroisoquinolines. This substrate promiscuity positions TfNCS as a highly promising enzyme for synthesizing fine chemicals. Understanding carbonyl-containing substrates' structural and electronic signatures that influence TfNCS activity can help expand its applications in the synthesis of different compounds and aid in protein optimization strategies. In this study, we investigated the influence of the molecular properties of aldehydes and ketones on their reactivity in the TfNCS-catalyzed Pictet-Spengler reaction. Initially, we compiled a library of reactive and unreactive compounds from previous publications. We also performed enzymatic assays using nuclear magnetic resonance to identify some reactive and unreactive carbonyl compounds, which were then included in the library. Subsequently, we employed QSAR and DFT calculations to establish correlations between substrate-candidate structures and reactivity. Our findings highlight correlations of structural and stereoelectronic features, including the electrophilicity of the carbonyl group, to the reactivity of aldehydes and ketones toward the TfNCS-catalyzed Pictet-Spengler reaction. Interestingly, experimental data of seven compounds out of fifty-three did not correlate with the electrophilicity of the carbonyl group. For these seven compounds, we identified unfavorable interactions between them and the TfNCS. Our results demonstrate the applications of in silico techniques in understanding enzyme promiscuity and specificity, with a particular emphasis on machine learning methodologies, DFT electronic structure calculations, and molecular dynamic (MD) simulations.


Assuntos
Aldeídos , Cetonas , Aldeídos/química , Aldeídos/metabolismo , Cetonas/química , Cetonas/metabolismo , Especificidade por Substrato , Carbono-Nitrogênio Ligases/metabolismo , Carbono-Nitrogênio Ligases/química , Thalictrum/enzimologia , Thalictrum/metabolismo , Thalictrum/química , Simulação de Dinâmica Molecular , Biocatálise
11.
PLoS One ; 19(5): e0301041, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701088

RESUMO

OBJECTIVE: To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. RESEARCH DESIGN AND METHODS: This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40-400 mg/dL, 2.2-22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4-8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. RESULTS: The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. CONCLUSIONS: The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. TRIAL REGISTRATION: Clinical trial identifier: NCT04782934.


Assuntos
Etanol , Estudos de Viabilidade , Cetonas , Ácido Láctico , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Cetonas/análise , Masculino , Etanol/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Feminino , Ácido Láctico/análise , Ácido Láctico/sangue , Glicemia/análise , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 1/sangue , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Glucose/análise
12.
Food Res Int ; 187: 114330, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763633

RESUMO

Processing technology plays a crucial role in the formation of tea aroma. The dynamic variations in volatile metabolites across different processing stages of fresh scent green tea (FSGT) were meticulously tracked utilizing advanced analytical techniques such as GC-E-Nose, GC-MS, and GC × GC-TOFMS. A total of 244 volatile metabolites were identified by GC-MS and GC × GC-TOFMS, among which 37 volatile compounds were concurrently detected by both methods. Spreading and fixation stages were deemed as pivotal processes for shaping the volatile profiles in FSGT. Notably, linalool, heptanal, 2-pentylfuran, nonanal, ß-myrcene, hexanal, 2-heptanone, pentanal, 1-octen-3-ol, and 1-octanol were highlighted as primary contributors to the aroma profiles of FSGT by combining odor activity value assessment. Furthermore, lipid degradation and glycoside hydrolysis were the main pathways for aroma formation of FSGT. The results not only elucidate the intricate variations in volatile metabolites but also offer valuable insights into enhancing the processing techniques for improved aroma quality of green tea.


Assuntos
Manipulação de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Chá , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Odorantes/análise , Chá/química , Manipulação de Alimentos/métodos , Nariz Eletrônico , Aldeídos/análise , Aldeídos/metabolismo , Monoterpenos Acíclicos/metabolismo , Monoterpenos Acíclicos/análise , Camellia sinensis/química , Camellia sinensis/metabolismo , Cetonas/análise , Cetonas/metabolismo , Octanóis
13.
Food Res Int ; 187: 114398, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763656

RESUMO

Nowadays, it is important to monitor the freshness of meat during storage to protect consumers' health. Volatile organic compounds (VOCs) are responsible for odour and taste of food, and they give an indication about meat quality and freshness. This study had the aim to seek and select potential new markers of meat spoilage through a semi-quantitative analysis in five types of meat (beef, raw and baked ham, pork sausage and chicken) and then to develop a new quantitative analytical method to detect and quantify potential markers on five types of meat simultaneously. Firstly, a new headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method was developed to evaluate the volatile profile of five types of meat, preserved at 4 °C for 5 days. Among the 40 compounds identified, 15 were chosen and selected as potential shelf-life markers on the basis of their presence in most of meat samples or/and for their constant increasing/decreasing trend within the sample. Afterwards, a quantitative HS-SPME-GC-MS analytical method was developed to confirm which VOCs can be considered markers of shelf-life for these meat products, stored at 4 °C for 12 days. Some of the compounds analyzed attracted attention as they can be considered markers of shelf-life for at least 4 types of meat: 1-butanol, 3-methylbutanol, 1-hexanol, 2-nonanone, nonanal, 1-octen-3-ol and linalool. In conclusion, in this study a new quantitative HS-SPME-GC-MS analytical method to quantity 15 VOCs in five types of meat was developed and it was demonstrated that some of the compounds quantified can be considered markers of shelf-life for some of the meat products analyzed.


Assuntos
Armazenamento de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Produtos da Carne , Microextração em Fase Sólida , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Sólida/métodos , Produtos da Carne/análise , Animais , Suínos , Odorantes/análise , Bovinos , Aldeídos/análise , Galinhas , Cetonas/análise , Pentanóis/análise , Monoterpenos Acíclicos/análise , Octanóis
14.
J Agric Food Chem ; 72(20): 11321-11330, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38714361

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase , Arabidopsis , Desenho de Fármacos , Inibidores Enzimáticos , Herbicidas , Simulação de Acoplamento Molecular , Herbicidas/química , Herbicidas/farmacologia , Herbicidas/síntese química , 4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , 4-Hidroxifenilpiruvato Dioxigenase/química , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Relação Estrutura-Atividade , Estrutura Molecular , Cetonas/química , Cetonas/farmacologia , Cetonas/síntese química , Cicloexanonas/química , Cicloexanonas/farmacologia , Cicloexanonas/síntese química , Triticum/química , Proteínas de Arabidopsis/antagonistas & inibidores , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo
15.
ACS Appl Bio Mater ; 7(6): 3981-3990, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38781457

RESUMO

Polyetheretherketone (PEEK), particularly its sulfonated form (SPEEK), has emerged as a promising synthetic biomaterial for artificial bone implants, providing an alternative to conventional titanium metal. However, postoperative infections pose a critical challenge, driven by diverse and antibiotic-resistant bacteria. To address this issue, we propose the modification of the SPEEK surface using a thin graphene oxide (GO) film containing silver (Ag) ions. The resulting coating exhibits substantial antibacterial effects against various pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Experimental assessments elucidate the coating's impact on bacterial adhesion, biofilm formation, and morphology. The results suggest that hindered bacterial growth stems from reduced biofilm production and the controlled release of Ag ions facilitated by the GO coating. The Ag/GO-SPEEK material holds promise as a bioactive implant, addressing the challenges associated with bacterial targeting in bone tissue engineering applications.


Assuntos
Antibacterianos , Benzofenonas , Grafite , Teste de Materiais , Testes de Sensibilidade Microbiana , Polietilenoglicóis , Polímeros , Prata , Grafite/química , Grafite/farmacologia , Prata/química , Prata/farmacologia , Benzofenonas/química , Benzofenonas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Polímeros/química , Polímeros/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Cetonas/química , Cetonas/farmacologia , Tamanho da Partícula , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos
16.
J Chromatogr A ; 1728: 464998, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38795423

RESUMO

Covalent organic frameworks (COFs) show promise as a stationary phase in high performance liquid chromatography (HPLC). However, there are only a few COFs-based stationary phases developed for HPLC separation so far. Therefore, it is crucial to not only develop more varieties of COFs-type stationary phases for HPLC separation, but also to explore the retention mechanism of solutes on these stationary phases. In this paper, a new in-situ growth method was developed to prepare ß-ketoenamine COF-TpPa-1@SiO2 composite microspheres, using spherical silica as the core material and COF-TpPa-1 fabricated by covalent conjugation of 1,3,5-triformylphloroglucinol (Tp) and p-phenylenediamine (Pa-1) as the COF shells. The resulting microspheres exhibit uniform morphology, good monodispersity, large specific surface area, narrow size distribution, and high stability. Due to diverse functional groups in the structure of COF-TpPa-1, the microspheres can offer multiple interactions, such as hydrophobic, π-π stacking and electron-donor-acceptor (EDA) between COFs and analytes. As a result, the COF-TpPa-1@SiO2 composite microspheres can be used as a mixed-mode stationary phase for HPLC separation. The chromatographic performance and retention mechanism of the COF-TpPa-1@SiO2 packed column were investigated by separating polar and non-polar solutes, as well as isomers, in various HPLC modes, including reversed-phase liquid chromatography (RPLC), hydrophilic interaction chromatography (HILIC), and RPLC/HILIC mixed-mode chromatography. The results showed successful separation of non-polar alkylbenzene homologues, polycyclic aromatic hydrocarbons (PAHs), and polar amines and phenols in RPLC mode. The "U-shaped" curves of retention factor with the ACN concentration in mobile phase for four nucleobases indicated that the solute retention on the column followed a mixed mode mechanism of RPLC/HILIC. Compared to a traditional C18 column, the COF-TpPa-1@SiO2 column exhibited superior separation efficiency, stability, repeatability and reproducibility in the separation of analytes with different polarities. The column enhanced the aromatic, shape and planar selectivity for PAHs and isomers through π-π interaction and improved the separation efficiency for electron-deficient compounds due to EDA effect. At last, the column was successfully used to separate and detect the residues of 5 phenylurea herbicides (PUHs) in soil. All these results indicate the potential of COFs for chromatography applications.


Assuntos
Cromatografia de Fase Reversa , Interações Hidrofóbicas e Hidrofílicas , Microesferas , Dióxido de Silício , Cromatografia Líquida de Alta Pressão/métodos , Dióxido de Silício/química , Cromatografia de Fase Reversa/métodos , Estruturas Metalorgânicas/química , Aminas/química , Aminas/isolamento & purificação , Cetonas
17.
J Mech Behav Biomed Mater ; 156: 106581, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38776740

RESUMO

Patient-specific fabrication of scaffold/implant requires an engineering approach to manufacture the ideal scaffold. Herein, we design and 3D print scaffolds comprised of polyether-ether-ketone (PEEK) and sodium-carboxymethyl cellulose (Na-CMC). The fabricated scaffold was dip coated with Zn and Mn doped bioactive glass nanoparticles (Zn-Mn MBGNs). The synthesized ink exhibit suitable shear-thinning behavior for direct ink write (DIW) 3D printing. The scaffolds were crafted with precision, featuring 85% porosity, 0.3 mm layer height, and 1.5 mm/s printing speed at room temperature. Scanning electron microscopy images reveal a well-defined scaffold with an average pore size of 600 ± 30 µm. The energy dispersive X-ray spectroscopy analysis confirmed a well dispersed/uniform coating of Zn-Mn MBGNs on the PEEK/Na-CMC scaffold. Fourier transform infrared spectroscopy approved the presence of PEEK, CMC, and Zn-Mn MBGNs. The tensile test revealed a Young's modulus of 2.05 GPa. Antibacterial assays demonstrate inhibition zone against Staphylococcus aureus and Escherichia Coli strains. Chick Chorioallantoic Membrane assays also present significant angiogenesis potential, owing to the antigenic nature of Zn-Mn MBGNs. WST-8 cell viability assays depicted cell proliferation, with a 103% viability after 7 days of culture. This study suggests that the PEEK/Na-CMC scaffolds coated with Zn-Mn MBGNs are an excellent candidate for osteoporotic fracture treatment. Thus, the fabricated scaffold can offer multifaceted properties for enhanced patient outcomes in the bone tissue regeneration.


Assuntos
Benzofenonas , Carboximetilcelulose Sódica , Vidro , Cetonas , Manganês , Nanopartículas , Polietilenoglicóis , Polímeros , Impressão Tridimensional , Staphylococcus aureus , Alicerces Teciduais , Zinco , Porosidade , Benzofenonas/química , Vidro/química , Cetonas/química , Cetonas/farmacologia , Alicerces Teciduais/química , Staphylococcus aureus/efeitos dos fármacos , Carboximetilcelulose Sódica/química , Nanopartículas/química , Zinco/química , Zinco/farmacologia , Polímeros/química , Manganês/química , Polietilenoglicóis/química , Antibacterianos/química , Antibacterianos/farmacologia , Animais , Escherichia coli/efeitos dos fármacos , Teste de Materiais , Humanos
18.
BMC Oral Health ; 24(1): 545, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730391

RESUMO

BACKGROUND: This Finite Element Analysis was conducted to analyze the biomechanical behaviors of titanium base abutments and several crown materials with respect to fatigue lifetime and stress distribution in implants and prosthetic components. METHODS: Five distinct designs of implant-supported single crowns were modeled, including a polyetheretherketone (PEEK), polymer-infiltrated ceramic network, monolithic lithium disilicate, and precrystallized and crystallized zirconia-reinforced lithium silicates supported by a titanium base abutment. For the static load, a 100 N oblique load was applied to the buccal incline of the palatal cusp of the maxillary right first premolar. The dynamic load was applied in the same way as in static loading with a frequency of 1 Hz. The principal stresses in the peripheral bone as well as the von Mises stresses and fatigue strength of the implants, abutments, prosthetic screws, and crowns were assessed. RESULTS: All of the models had comparable von Mises stress values from the implants and abutments, as well as comparable maximum and minimum principal stress values from the cortical and trabecular bones. The PEEK crown showed the lowest stress (46.89 MPa) in the cervical region. The prosthetic screws and implants exhibited the highest von Mises stress among the models. The lithium disilicate crown model had approximately 9.5 times more cycles to fatique values for implants and 1.7 times more cycles to fatique values for abutments than for the lowest ones. CONCLUSIONS: With the promise of at least ten years of clinical success and favorable stress distributions in implants and prosthetic components, clinicians can suggest using an implant-supported lithium disilicate crown with a titanium base abutment.


Assuntos
Benzofenonas , Coroas , Dente Suporte , Prótese Dentária Fixada por Implante , Análise do Estresse Dentário , Análise de Elementos Finitos , Titânio , Titânio/química , Humanos , Porcelana Dentária/química , Polietilenoglicóis/química , Materiais Dentários/química , Polímeros , Cetonas/química , Zircônio/química , Implantes Dentários para Um Único Dente , Teste de Materiais , Projeto do Implante Dentário-Pivô , Fenômenos Biomecânicos
19.
Nutrients ; 16(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38794716

RESUMO

It has been demonstrated that isoflurane-induced anesthesia can increase the blood glucose level, leading to hyperglycemia and several adverse effects. The administration of a mix of ketone diester (KE) and medium-chain triglyceride (MCT) oil, named KEMCT, abolished the isoflurane-anesthesia-induced increase in blood glucose level and prolonged the recovery time from isoflurane anesthesia in a male preclinical rodent model, Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. While most preclinical studies use exclusively male animals, our previous study on blood glucose changes in response to KEMCT administration showed that the results can be sex-dependent. Thus, in this study, we investigated female WAG/Rij rats, whether KEMCT gavage (3 g/kg/day for 7 days) can change the isoflurane (3%)-anesthesia-induced increase in blood glucose level and the recovery time from isoflurane-evoked anesthesia using the righting reflex. Moreover, KEMCT-induced ketosis may enhance both the extracellular level of adenosine and the activity of adenosine A1 receptors (A1Rs). To obtain information on the putative A1R mechanism of action, the effects of an A1R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine; intraperitoneal/i.p. 0.2 mg/kg), on KEMCT-generated influences were also investigated. Our results show that KEMCT supplementation abolished the isoflurane-anesthesia-induced increase in blood glucose level, and this was abrogated by the co-administration of DPCPX. Nevertheless, KEMCT gavage did not change the recovery time from isoflurane-induced anesthesia. We can conclude that intragastric gavage of exogenous ketone supplements (EKSs), such as KEMCT, can abolish the isoflurane-anesthesia-induced increase in blood glucose level in both sexes likely through A1Rs in WAG/Rij rats, while recovery time was not affected in females, unlike in males. These results suggest that the administration of EKSs as an adjuvant therapy may be effective in mitigating metabolic side effects of isoflurane, such as hyperglycemia, in both sexes.


Assuntos
Anestésicos Inalatórios , Glicemia , Isoflurano , Cetonas , Animais , Feminino , Isoflurano/farmacologia , Isoflurano/administração & dosagem , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Ratos , Cetonas/administração & dosagem , Cetonas/farmacologia , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Ratos Wistar , Suplementos Nutricionais , Triglicerídeos/sangue , Triglicerídeos/administração & dosagem , Masculino , Adenosina/farmacologia , Adenosina/administração & dosagem , Anestesia/métodos
20.
BMC Surg ; 24(1): 169, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811965

RESUMO

BACKGROUND: Whether polyetheretherketone (PEEK) rods have potential as an alternative to titanium alloy (Ti) rods in transforaminal lumbar interbody fusion (TLIF) remains unclear, especially in cases with insufficient anterior support due to the absence of a cage. The purpose of this study was to investigate biomechanical differences between PEEK rods and Ti rods in TLIF with and without a cage. METHODS: An intact L1-L5 lumbar finite element model was constructed and validated. Accordingly, four TLIF models were developed: (1) Ti rods with a cage; (2) PEEK rods with a cage; (3) Ti rods without a cage; and (4) PEEK rods without a cage. The biomechanical properties were then compared among the four TLIF constructs. RESULTS: With or without a cage, no obvious differences were found in the effect of PEEK rods and Ti rods on the range of motion, adjacent disc stress, and adjacent facet joint force. Compared to Ti rods, PEEK rods increase the average bone graft strain (270.8-6055.2 µE vs. 319.0-8751.6 µE). Moreover, PEEK rods reduced the stresses on the screw-rod system (23.1-96.0 MPa vs. 7.2-48.4 MPa) but increased the stresses on the cage (4.6-35.2 MPa vs. 5.6-40.9 MPa) and endplates (5.7-32.5 MPa vs. 6.6-37.6 MPa). CONCLUSIONS: Regardless of whether a cage was used for TLIF, PEEK rods theoretically have the potential to serve as an alternative to Ti rods because they may provide certain stability, increase the bone graft strain, and reduce the posterior instrumentation stress, which might promote bony fusion and decrease instrumentation failure.


Assuntos
Ligas , Benzofenonas , Análise de Elementos Finitos , Cetonas , Vértebras Lombares , Polietilenoglicóis , Polímeros , Fusão Vertebral , Titânio , Humanos , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Fenômenos Biomecânicos , Vértebras Lombares/cirurgia , Amplitude de Movimento Articular , Materiais Biocompatíveis
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